Nothing Special   »   [go: up one dir, main page]

EP3835718B1 - Vorrichtung zur bereitstellung mikrooptischer kohärenztomographie in einem atmungssystem - Google Patents

Vorrichtung zur bereitstellung mikrooptischer kohärenztomographie in einem atmungssystem Download PDF

Info

Publication number
EP3835718B1
EP3835718B1 EP21151195.1A EP21151195A EP3835718B1 EP 3835718 B1 EP3835718 B1 EP 3835718B1 EP 21151195 A EP21151195 A EP 21151195A EP 3835718 B1 EP3835718 B1 EP 3835718B1
Authority
EP
European Patent Office
Prior art keywords
exemplary
μoct
mucus
sample
image
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP21151195.1A
Other languages
English (en)
French (fr)
Other versions
EP3835718A1 (de
Inventor
Steven M. ROWE
Guillermo J. Tearney
Brett Eugene Bouma
Linbo Liu
Eric J. Sorscher
Kengyeh Ken CHU
Bradford James Diephuis
Eric James WILSTERMAN JR.
Gregory Andrew DIRKSEN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
General Hospital Corp
UAB Research Foundation
Original Assignee
General Hospital Corp
UAB Research Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by General Hospital Corp, UAB Research Foundation filed Critical General Hospital Corp
Publication of EP3835718A1 publication Critical patent/EP3835718A1/de
Application granted granted Critical
Publication of EP3835718B1 publication Critical patent/EP3835718B1/de
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/02041—Interferometers characterised by particular imaging or detection techniques
    • G01B9/02044—Imaging in the frequency domain, e.g. by using a spectrometer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/02049—Interferometers characterised by particular mechanical design details
    • G01B9/0205—Interferometers characterised by particular mechanical design details of probe head
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/0209—Low-coherence interferometers
    • G01B9/02091—Tomographic interferometers, e.g. based on optical coherence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/45—Interferometric spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J9/00—Measuring optical phase difference; Determining degree of coherence; Measuring optical wavelength
    • G01J9/02—Measuring optical phase difference; Determining degree of coherence; Measuring optical wavelength by interferometric methods
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution
    • G01N15/0205—Investigating particle size or size distribution by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
    • G01N21/45—Refractivity; Phase-affecting properties, e.g. optical path length using interferometric methods; using Schlieren methods
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4788—Diffraction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N29/00—Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/12—Generating the spectrum; Monochromators
    • G01J3/18—Generating the spectrum; Monochromators using diffraction elements, e.g. grating
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/30—Measuring the intensity of spectral lines directly on the spectrum itself
    • G01J3/36—Investigating two or more bands of a spectrum by separate detectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/45—Interferometric spectrometry
    • G01J3/453—Interferometric spectrometry by correlation of the amplitudes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
    • G01N11/10—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by moving a body within the material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
    • G01N2011/006—Determining flow properties indirectly by measuring other parameters of the system
    • G01N2011/008—Determining flow properties indirectly by measuring other parameters of the system optical properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G01N2021/653—Coherent methods [CARS]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G01N2021/653—Coherent methods [CARS]
    • G01N2021/655—Stimulated Raman
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy

Definitions

  • Exemplary embodiments of the present disclosure relate to methods, systems, arrangements and computer-accessible medium for providing micro-optical coherence tomography procedures, and more particularly to exemplary methods, systems, arrangements and computer-accessible medium for analyzing respiratory airways and other ciliated tissues using micro-optical coherence tomography procedures.
  • the human lung is suited for providing gas exchange from the atmosphere to the body: with every breath, oxygen enters the bloodstream, and carbon dioxide is removed.
  • This constant environmental exposure makes the defense systems of the lung extremely important in maintaining health and preventing disease.
  • the surface epithelial cells which line the lung are protected by a tightly regulated layer of mucus which functions to entrap pathogens and inhaled particulates. These cells also contain tiny hair-like projections called cilia which propel the semi-liquid mucus gel layer out of the lung.
  • This system commonly called the mucociliary clearance (MCC) apparatus, facilitates the lung to entrap and clear particles and pathogens which enter the lung from the environment.
  • MCC mucociliary clearance
  • Cilia are complex in structure, with outer and inner rings of microtubules which propel the cilia in specific beat patterns that are also coordinated with one another.
  • Other parts of the apparatus are similarly complex, including the content and molecular makeup and the electrolyte and water content of the mucus gel layer, which determine its physical characteristics and transportability.
  • cystic fibrosis is the most common lethal genetic disease in the Caucasian population, and is a significant cause of morbidity and early mortality from progressive lung disease.
  • CFTR cystic fibrosis transmembrane regulator
  • MCC mucociliary clearance
  • ASL airway surface liquid
  • PCL periciliary liquid layer
  • PCD primary ciliary dyskinesia
  • COPD chronic obstructive pulmonary disease
  • Other common lung diseases are also affected by dysfunction of the epithelial surface, including, but not limited to, types of interstitial lung disease such as its most common form idiopathic pulmonary fibrosis which are characterized by abnormal function of the surface mucins, the proteins that form the mucus gel.
  • Mucus itself can be characterized in part by its viscosity, or its resistance to physical flow. Thicker, more viscous mucus is more difficult for the mucociliary apparatus to clear, contributing to disease.
  • the study of viscosity by rheology measurements allows for characterizing mucus physical properties, understanding mechanisms of human disease, and evaluating the effect of therapeutics to address abnormal mucus. May studies have shown that expectorated sputa from CF patients are abnormal, demonstrating a highly viscous nature and increased percentage of solid content.
  • Mucus is also characterized by its adherence. Abnormal adherence to the surface structures of the airway are thought to substantially contribute to clinical disease.
  • ASL height can be measured in vitro using confocal microscopy by aid of fluorescent staining, but is technically challenging, difficult to achieve the high axial resolution required to accurately assess ASL/PCL, and prone to artifacts caused by interference or removal of the native fluid and flow by the exogenous contrast agents.
  • MCT mucociliary transport
  • CBF ciliary beat frequency
  • ASL ciliary beat frequency
  • PCL ciliary beat frequency
  • OCT optical coherence tomography
  • the technology uses the reflectance signature of near-infrared light to permit real-time imaging with cellular level detail, and has been employed successfully for microscopic analysis of coronary artery and esophageal mucosa by the endoscopic approach in living human subjects.
  • OCT uses coherence gating for optical sectioning to attain an axial resolution or section thickness ranging from 1-10 ⁇ m.
  • OCT is not reliant on a high numerical aperture lens, it can employ an imaging lens with a relatively large confocal parameter, facilitating a greater penetration depth (about 1 mm) and a cross-sectional display format.
  • OCT is particularly well suited for non-invasive microscopy in cells and tissues since it can be implemented via small, flexible probes, does not require contact with the cell surface or use of contrast medium, and acquires high resolution images with very rapid acquisition times and flexible focal range.
  • micro-OCT micro-OCT
  • ⁇ OCT With ⁇ OCT, high-resolution ranging is conducted in tissue by detecting spectrally resolved interference between the tissue sample and a reference.
  • ⁇ OCT can utilize a high-speed linear camera, it is capable of capturing images at more than 50 million pixels per second, which is approximately two orders of magnitude faster than conventional time-domain OCT systems.
  • Wojtkowski M. et al. “Three-dimensional Retinal Imaging with High-Speed Ultrahigh-Resolution Optical Coherence Tomography", Ophthalmology 2005 ).
  • ⁇ OCT images can be obtained in vivo with an axial resolution of approximately 2 ⁇ m, which is adequate to visualize the PCL, beating cilia, and mucosal glands.
  • High throughput screening (HTS) for exemplary modulators of epithelial function has been successful as a drug discovery modality, identifying certain small molecules, biologics, and pathways relevant to human airway disease. While this is been particularly successful in CF to identify modulators of CFTR, the assay systems typically used are limited in scope, and cannot directly interrogate epithelial function relevant to mucociliary transport in humans. Rather, these approaches are reductionist towards specific pathways that may or may not be directly relevant to a broad array of human diseases. For example, almost all HTS technologies for CF attempt to identify alterations in chloride, halide, or sodium transport, and can only probe one of these pathways depending on the specific probe. This reductionist approach makes the assay limited in scope, and is relevant only to diseases where that ion transport pathway is relevant.
  • ⁇ OCT arrangement For example, with the use of ⁇ OCT arrangement, one can provide a high spatial resolution and frame rate reported to date.
  • Cross-sectional images of tissue can be acquired at about 44 frames per second (fps) at an axial resolution of 1.5 ⁇ m and a transverse resolution of 2 ⁇ m.
  • the size of a typical ⁇ OCT image can be about 3 mm ⁇ 0.6 mm.
  • Such arrangement can facilitate, e.g., a simultaneous and high-resolution acquisition of ciliary beating (respiratory epithelium as well as other tissue types), ASL and PCL depths, and mucus transport in living, full thickness airway cells and tissues, and provides a quantitative measurement while also visualizing anatomy, without use of contrast dyes or other experimental manipulations.
  • Such arrangement can also be used simultaneously with dual fluorescence imaging. It is possible to acquire both fluorescence and structural/functional ⁇ OCT information simultaneously, from the same location on the sample.
  • chloride and bicarbonate influx can be measured and related to co-localized ASL, CBF, MCT and mucus rheology.
  • the exemplary ⁇ OCT arrangement in accordance with the invention is using natural particles facilitating tracking for mucus microrheology which can be significant; and also providing for the measurement to be obtained for in living subjects in situ.
  • the mucus properties can be determined simultaneously and co-localized with the structural functional parameters of MCC, and the findings are not subject to artifacts caused by adding exogenous particles to the mucus.
  • the ⁇ OCT arrangement can provide a more robust assay that identifies multiple epithelial functions simultaneously.
  • Each of these functions can be directly relevant to human physiology, thus is much more likely to translate effectively to a broader array of human disease.
  • screens can be established for ciliary function, altered mucus viscosity, or hydrators of the mucus, depending on the purpose of the screen. This represents a major advantage over prior screens.
  • the assay can also be established as a robust means to provide secondary characterization of drugs, molecules, or biologics and their effects on human physiology. At present, there may not be secondary assay that directly correlates with key functions of the epithelial surface. The direct assessment of surface epithelial functional testing can provide much greater predictive accuracy regarding the success of a novel agent in clinical testing. Because the ⁇ OCT arrangement can be suitable for use in cell culture, tissue culture, or in vivo use in animal models or humans (see also below), the assay can provide secondary evaluation in a variety of primary, secondary, and tertiary model systems, and is unique in this regard. Additionally, it can be suitable for human proof of concept testing, providing an approach with unprecedented experimental continuity across model systems.
  • the exemplary ⁇ OCT arrangement according to the invention can be used in vivo in human subjects. It is possible to provide an exemplary pulmonary ⁇ OCT probe that can have a high enough resolution to visualize respiratory cells, cilia, and native microparticle motion to determine mucus viscosity. For these purposes, the exemplary ⁇ OCT arrangement in accordance with the invention can use a transverse resolution of 2-3 ⁇ m over an extended depth-of-field, or focal range. Using conventional optics, this focal range can be maintained by no greater than 50 ⁇ m.
  • This focal range can be too small for cross-sectional imaging of the airways in vivo, which generally requires a focal range of approximately 500 ⁇ m in order to accommodate the diversity of probe-to-tissue distances across a reasonable field of view on a typically uneven surface of an in vivo subject.
  • the exemplary embodiments of imaging probes described herein can illuminate an extended axial focus and contain a reference mirror for the interferometer.
  • certain exemplary embodiments of the probe optics according to the present disclosure can be coupled to the subject via an exemplary balloon or wire baskets associated with the outer sheath of the probe.
  • the exemplary ⁇ OCT arrangement can be used for investigating ciliary function disclosed herein are also applicable in organ systems inside and outside of the respiratory system in both humans and animals. Many other tissues contain ciliated cells, including but not limited to the Fallopian tubes of the female reproductive tract, sperm produced by the male reproductive tract, the ependyma of the brain, the photoreceptor cells of the eye, the renal tubules within the kidney, and embryonic cells which regulate organ formation and development.
  • ciliary abnormalities include, among others, human disease such as infertility (both male- and female-related causes), hydrocephalus and other congenital malformations of the brain including neuronal migration disorders, Bardet-Biedl syndrome and other causes of blindness, polycystic kidney disease, situs inversus and associated congenital heart diseases, and many other identified or suspected ciliopathies.
  • ⁇ OCT can be applied to these other ciliated tissue structures as well, leading to new understanding and potential therapies for many devastating diseases.
  • the exemplary imaging platform can utilize optical reflectance depth profiles, images, volumes, or movies of respiratory and/or ciliated cells, tissues, or organs, including their secretions and immediate environment, using the exemplary ⁇ OCT technology.
  • such technology can facilitate functional dynamic movements of cellular components, including cilia.
  • An exemplary ⁇ OCT arrangement can be used for high throughput screening (HTS).
  • HTS is a procedure of drug discovery in which a library of compounds is studied using automated methods to determine which, if any, are active for the outcome being studied.
  • the exemplary underlying properties of ⁇ OCT including its rapid acquisition time, non-invasive technique, and wide focal range make it a highly suitable technology for medium to high throughput screening methods.
  • Further therapeutic drug screening programs have been provided that can use airway surface liquid depth as a principal readout, and agents that target CFTR or other ion transport pathways are prioritized based on preclinical use of this exemplary measurement.
  • the exemplary high throughput screening platform can also be combinable with simultaneous and co-registered fluorescence confocal imaging.
  • Fluorescent markers enable dynamic assays of intracellular ion concentrations such as calcium and bicarbonate, which complements the exemplary ⁇ OCT data to provide an even more powerful tool for interrogation of epithelial physiology and evaluation of ciliary disease treatments.
  • Exemplary computer procedures developed for the analysis of ⁇ OCT high throughput screening output images are employed to extract relevant parameters such as airway surface liquid depth, mucociliary transport rate, and ciliary beat frequency. These measurements are performed automatically with minimal user intervention to maximize throughput.
  • a quality control procedure can remove spurious measurements and outliers, while the measurements from unrejected trials are aggregated, yielding final results.
  • the exemplary ⁇ OCT arrangement can also be well suited for secondary characterization of agents preliminarily identified to be active in airway epithelia. Results will help elucidate the relationship between ASL regulation, cilia beating, and mucus propulsion, and establish functional profiles for compounds identified by earlier drug screening programs. Secondary evaluation of ion transport agents known to be active in airway epithelia assist to clarify relationship(s) between sodium and chloride channel activity, airway surface liquid regulation, ciliary activity, and mucus transport.
  • the exemplary equipment can be suitable for imaging explanted lung tissues for validation in the intact airway.
  • Tissues can be derived from donated human lung tissue, or from experimental animal models of both lung health and various lung diseases.
  • ex vivo tissues allows for environmental control and direct applications of various agents, allowing for proof of concept work prior to direct in vivo human applications.
  • Mucus rheology is analyzed using the exemplary ⁇ OCT arrangement in accordance with the invention.
  • CF sputum generally exhibits increased viscosity when monitored by exogenous particle tracking microrheology, an exemplary technique in which the mean squared displacements (MSD) of fluorescent microparticles are measured and converted to viscosity by the generalized Stokes-Einstein relation (GSER).
  • MSD mean squared displacements
  • GSER generalized Stokes-Einstein relation
  • the ⁇ OCT probes can be used in vivo to monitor the earliest features of pulmonary decline in disease such as cystic fibrosis. Monitoring patients before disease progression occurs can provide key information in the study of disease including key information regarding the anatomic and physical relationships of mucociliary clearance. Additionally, the exemplary ⁇ OCT probe can be used in context of suspicion of known and unknown diseases to evaluate for disorders affecting the functional airway microanatomy, and to precisely characterize specific abnormalities seen in individual patients.
  • exemplary apparatus can be provided for obtaining data regarding a plurality of samples. For example, using at least one arrangement, it is possible to receive interferometric information that is based on radiations provided from a reference and the samples that are provided in respective chambers.
  • the arrangement(s) can comprise at least one optical configuration which is configured to focus at least one electromagnetic radiation on the samples.
  • a depth range of the focus of the electromagnetic radiation(s) caused by the optical configuration(s) can be greater than a confocal parameter associated with a spot size of the focus.
  • the optical configuration(s) can include an axicon lens arrangement, a binary apodization element, a phase apodization element, a refractive optical element, an annulus, and/or a diffractive element.
  • the arrangement(s) can also comprise a confocal arrangement, a florescence arrangement, Raman arrangement, an infrared arrangement, spectrascopicn arrangement, a multiphoton arrangement, a multiharmonic arrangement, a nonlinear microscopy arrangement, a CARS SRS arrangement, or an ultrasound arrangement.
  • each of the respective chambers can have an agent which can be different from or same as another one of the agents.
  • the arrangement(s) can be further configured to obtain the data using the interferometric information based on an interaction of the agents with the samples.
  • One of the agents and another one of the agents (i) can differ from one another in a quantity or a concentration thereof, and/or (ii) are applied at different time periods within the respective chambers.
  • At least one of the samples can include a living cell, and/or a cilia.
  • a method can be provided for obtaining data regarding a plurality of samples. For example, it is possible to receive interferometric information that is based on radiation provided from a reference and the samples that are provided in respective chambers. Further, based on the interferometric information, it is possible to discriminate between agents to identify a particular agent that effects a particular function within at least one of the samples.
  • the particular function can include motion, and/or the particular agent can have at least one characteristic that is beneficial for a treatment of cystic fibrosis.
  • a method can be provided for reviewing therapeutic agents.
  • samples can be prepared, and manipulated to increase amount or viability thereof.
  • At least one of the samples can be placed in at least one respective chamber.
  • the chambers can be scanned using at least one arrangement which can be configured to receive interferometric information that is based on radiation provided from a reference and the at least one sample.
  • At least one of the agents can be selected based on the scanning and the interferometric information.
  • At least one of the samples can includes epithelial cells that have been dissected from a whole lung sample and expanded in flasks.
  • the apparatus is provided for obtaining data regarding at least one sample.
  • the apparatus includes at least one arrangement which can receive interferometric information that is based on radiation provided from a reference and the sample.
  • This exemplary arrangement is configured to (i) obtain dynamic tracking data regarding particles associated with the sample(s) using the interferometric information, and (ii) determine biomechanical properties of the sample(s) using the dynamic tracking data .
  • the particles can (i) include added and intrinsic particles to the at least one sample, and/or have a diameter that is less than 1 micron, 2 microns, or 5 microns.
  • the sample(s) includes mucus, and the particles include inclusions in the mucus.
  • the dynamic tracking data can include a measurement of a displacement and/or a size of at least one of the particles.
  • FIG. 1 An exemplary ⁇ OCT system is shown in Figure 1 .
  • light, beam and/or other electro-magnetic radiation from a broadband source 100 can be collimated by a lens 105 and attenuated by a neutral density filter 110.
  • the collimated, attenuated light/beam/radiation can pass through a beam splitter 115 before it is focused by a lens 120 onto a single mode fiber optic patch cable 125, and transmitted to an interferometer where it is re-collimated with lens 130.
  • the center of the collimated beam can be redirected with, e.g., a 45° rod mirror 135 through a neutral density filter 140 and objective lens 145 where it is focused onto a reference mirror 150.
  • the light/beam/radiation not redirected by the rod mirror 135 can form an annulus 155, and can pass through a transparent window 160 and a two dimensional scanning galvanometer 165 before being focused by an objective lens 170 onto a sample.
  • Light/beam/radiation reflected back from the sample 175 can be collected in the objective lens 170, passes back through the galvanometer 160 and the window 165 before being recombined with light reflected from the reference mirror 150.
  • the recombined light/beam/radiation can now contain interferometric information.
  • the returning light/beam/radiation can be focused onto the single mode fiber optic cable 125 by a lens 130.
  • the light/beam/radiation can be transmitted through the cable 125 and re-collimated by a lens 120 where it then passes through a beam splitter 115.
  • the collimated light/beam/radiation can be separated into its spectral components by a diffraction grating 180 and focused by a lens 185 onto a detection array 190, thus likely creating one A-line of interferometric information.
  • Such interferometric information can be transmitted from the detector 190 to an image acquisition device 191, and then to a computer 192 where the data can undergo processing for a display 195 and storage 194.
  • the computer 192 can additionally output analog and/or digital signals 193 to control various parts of the device including the light source 100, the galvanometers 160, and the camera 192, and/or other peripheral devices not shown.
  • Figures 2a-2d show exemplary imaging results from the exemplary ⁇ OCT procedure applied to respiratory epithelial cells.
  • HBE normal human bronchial epithelial
  • FIGs. 2a-2d in a time-averaged image of normal human bronchial epithelial (HBE) cells, e.g., distinct layers of air (203), mucus (206), cilia (209), PCL (215) and epithelium (218) can be visualized, and the morphology matches the inset image 221, a H&E stained sample of the same type.
  • HBE normal human bronchial epithelial
  • the ASL depth (200) and PCL depth (209) can be measured.
  • a scan of CF-afflicted newborn piglet trachea shows similar features, including the lumen (269), cilia (266), epithelium (278), lamina intestinal (284), and gland duct (281), but measured PCL depth (269) and ASL depth (272) are depleted.
  • Figure 3 shows a set of illustrations which indicates the capacity of the exemplary ⁇ OCT arrangements to analyze an active ciliary motion.
  • the top row (300) of Figure 3 illustrates a schematic of stages of ciliary motion during the full ciliary beat cycle.
  • Exemplary cross-sectional ⁇ OCT images of a cilium at two positions are presented in row 310 in columns A and B, as well as a time-averaged (4 seconds) recording in column C showing an arc indicating the effective strokes (312) and bilobular pattern of the recovery stroke (314).
  • Scale bars are 10 ⁇ m.
  • the ciliary motion pattern can be easily identified in the M-mode image of the active epithelial area shown at 320.
  • Corresponding time-lapse intensity analysis (330) reveals triphasic pattern of the ciliary beat cycle: the recovery stroke (blue line, 350), the effective stroke (orange line, 340) and the rest phase in between the effective stroke and next effective stroke.
  • FIGs 4a -4d show additional exemplary results from the exemplary ⁇ OCT arrangements applied to ciliary motion, as well as illustrative diagrams.
  • each ciliary beat cycle can start with a recovery stroke followed by an effective stroke.
  • a bend can be propagated up the cilium causing the cilium to rotate backwards in a clockwise sweep in a zone beneath the mucus as depicted in a schematic (see Figure 4a , 400) from a perspective view.
  • the cilium can progress immediately into the effective stroke, in which the cilia describes an arc of almost 110° in the cross-sectional plane and in the mucus transport direction (see Figures 4b and 4c, top panels) before reaching the rest phase.
  • Alteration in duration of cilia in the effective stroke, the recovery stroke or the resting state can reflect response to stimulation and has significant effect on mucociliary clearance in addition to CBF itself.
  • the exemplary ⁇ OCT images can provide a way to analyse the relative state of ciliary activity.
  • cilia tips appears as high intensity aggregated point scatterers, and because of the bend, the cilia tips appears at lower (e.g., 3-5 ⁇ m from the apical cell surface) position during the recovery stroke (see Figure 4a , 410) than in the effective stroke (see Figure 4b, 410) when cilia extend to their full length of ⁇ 7 ⁇ m and described an arc of 109° with radius about 7 ⁇ m along the direction of the mucus transport.
  • An exemplary time-averaged cross-sectional ⁇ OCT image - see Figure 4c, 410 - demonstrates typical ciliary beat pattern seen in the exemplary ⁇ OCT images, which is characterized by an arc pattern 412 with a peak about 7 ⁇ m above the apical cell surface (see light arrow) and a bilobular pattern 414 with about 3-5 ⁇ m above the apical cell surface and just below the arc, indicating recovery strokes .
  • M-mode view of the exemplary ⁇ OCT cilia images 420 time-lapse ciliary motion can be clearly seen which can be used to characterize metachony wave of the ciliary motion.
  • the exemplary signal intensity and duration 430 of the effective stroke and recovery stroke might reflect the status of the exemplary ciliary activity or ciliary load.
  • FIG. 5 shows exemplary results of images from the exemplary ⁇ OCT imaging procedure of non-respiratory tissue in murine and porcine animal models.
  • Cilia 500 appear as high intensity aggregated point scatterers in the low intensity background representing cerebrospinal fluid 510.
  • the ependymal epithelium 520 has a lower intensity than that of cilia but higher than that of the cerebrospinal fluid.
  • oviduct cilia 530 can appear as high intensity aggregated point scatterers.
  • the oviduct epithelium 540 can have a lower intensity than that of the oviduct cilia.
  • Figure 6 shows exemplary results of images from the exemplary ⁇ OCT imaging procedure of ex vivo porcine trachea tissue.
  • mucus gland and gland duct 610 within lamina intestinal 620 can also be seen in the exemplary ⁇ OCT images.
  • a thin liquid layer 630 at the duct surface can be seen surrounding the mucus 650.
  • 3D reconstruction of the exemplary ⁇ OCT image allows estimation of the gland duct cross-sectional area in the mucus transport, so that mucus transport rates of luminal contents can be estimated by multiplying the gland duct cross-sectional area with the longitudinal extrusion rates of mucus estimated from the real-time cross-sectional images.
  • animal models including but not limited to genetic or exposure induced models of disease are generated.
  • studies involving human subjects in the context of proof of concept clinical trials are obtained and/or utilized.
  • a treatment with compounds selected for secondary evaluation and/or mechanistic studies is performed.
  • experimental treatment is conducted, and in block 750, ⁇ OCT imaging can be performed.
  • Block 750 can be performed in vivo (via an endoscopic or rigid ⁇ OCT probe) or ex vivo (in the case of animal studies requiring sacrifice and extraction of tissues) imaging.
  • exemplary ⁇ OCT based endpoints can then be derived, and in block 770, data can then be prioritized and analyzed based on the biological question to be addressed and an informatics system to handle redundant data, ultimately resulting in final results in block 780.
  • an exemplary probe should be used to provide imaging access to the tissue of analysis.
  • a diagram of an exemplary embodiment of a ⁇ OCT probe is shown in Figure 8 .
  • This exemplary probe can be used in the human nose (rhinoscopy).
  • the exemplary probe can be contained within an outer tube (815) that remains statically positioned relative to the object or tissue to be imaged.
  • the optical components of the exemplary probe can be mounted within an inner shuttle tube (805), and mechanically driven in a longitudinal fashion relative to the outer tube via a rigid drive shaft (800).
  • the optical fiber (830) can deliver illumination into and collects reflected light from the imaging probe.
  • the fiber can be mechanically fixed to the drive shaft by the ferrule (810).
  • a 2mm spacer (835) can facilitate a divergence of the light from the fiber before collimation and focusing by the gradient-index lens (840).
  • the beam splitter (845) can comprise a glass cube with a diagonal reflective surface with a small elliptical region in the center that transmits light. This transmitted portion can be incident on a reflector (850), which can serve as the reference mirror for OCT.
  • the light reflected from the beamsplitter can be directed through a transparent window in the outer tube (820) towards the object or tissue to be imaged.
  • FIG. 9 A diagram of another exemplary embodiment of the ⁇ OCT probe is shown in Figure 9 .
  • This exemplary probe of Figure 9 can also be used in human or animal airways.
  • the optical components can be contained within a sheath (930) and stabilized against the lumen of the airway to be imaged by a wire basket (905).
  • An optical fiber (940) can deliver illumination into and collects reflected light from the imaging probe.
  • the fiber can be mechanically fixed to a drive shaft (935), which can provide longitudinal scanning of the optics within the sheath.
  • the illumination from the fiber 940 can be collimated in a hollow-centered pattern by means of a double-axicon GRIN lens (900), and then focused by a conventional GRIN lens (910).
  • a beamsplitter (915) can reflect a portion of the illumination light towards the object or tissue to be imaged, and can facilitate the remaining light to be transmitted to a reference mirror (945), which can be attached to a linear actuator (920) to facilitate for a positional adjustment.
  • the beamsplitter can also combine the light/beam/radiation reflected from the reference mirror and the sample.
  • FIG. 10 A diagram of yet another exemplary embodiment of the ⁇ OCT probe is shown in Figure 10 .
  • This exemplary probe of Figure 10 can also be used in human or animal airways, and contains the added features of a perfusion channel and electrode for performing electrical potential difference measurements.
  • the optical components can be contained within an insulating sheath (1055).
  • An optical fiber (1010) can deliver illumination into and collects reflected light from the imaging probe.
  • the fiber can be mechanically fixed to a drive shaft (1015), which provides longitudinal scanning of the optics within the sheath.
  • a bearing (1020) can center the shaft while enabling smooth linear motion of the shaft within the sheath.
  • the illumination from the fiber is collimated in a hollow-centered pattern using a double-axicon GRIN lens (1045), and then focused by a conventional GRIN lens (1025).
  • a beamsplitter (1030) can reflect a portion of the illumination light towards the object or tissue to be imaged, and can facilitate the remaining light to be transmitted to a reference mirror (1050). The beamsplitter can also combine the light reflected from the reference mirror and the sample.
  • a perfusion channel (1000) can facilitate liquid solutions to be delivered to the end of the probe, and an electrode channel (1005) can facilitate electrical recordings to be made.
  • One of the exemplary applications of the exemplary ⁇ OCT arrangement not covered by the claims is a high-throughput drug screening to analyze the effects of treatment compounds on respiratory epithelium.
  • a high-throughput flow diagram of such exemplary application is shown in Figure 11 and described as follows.
  • a growth of differentiated airway cells on air liquid interface is followed.
  • cells are treated with 1130 compound libraries, biologic libraries (e.g. siRNA, miRNA, etc.), alone and in combination with other agents.
  • compounds are selected which are chosen for known or proposed effects, prior screening hits, or mechanistic characterization.
  • cells are non-invasively imaged with the exemplary ⁇ OCT procedure using the exemplary HTS apparatus, with and without addition of known acute acting stimulants/inhibitors of ion transport for an additional test of additivity or specificity.
  • output of the exemplary ⁇ OCT automated procedures are used - which are multiple distinct but complementary measures of functional microanatomy, including ASL depth, PCL depth, CBF, MCT, microrheology properties (including but not limited to viscosity), effective stroke to recovery stroke ratio of loaded cilia, and estimates of cell viability.
  • fluorescent probes can also be assayed as an indicator of a molecular target, such as ion transport.
  • the cell culture plate can be transferred to a separate ion transport assay instrument, capable of measuring transepithelial voltage, transepithelial resistance, and calculating equivalent current, each traditional measures of transepithelial ion transport, which can be combined with OCT-based studies as an independent test in the same wells.
  • a separate ion transport assay instrument capable of measuring transepithelial voltage, transepithelial resistance, and calculating equivalent current, each traditional measures of transepithelial ion transport, which can be combined with OCT-based studies as an independent test in the same wells.
  • data can then be prioritized and analyzed based on the biological question to be addressed and an informatics system to handle redundant data, ultimately resulting in final results in block 1195.
  • Figure 12 shows a diagram of a high-throughput screening configuration using the exemplary ⁇ OCT system illustrated in Figure 1 .
  • the apodized light from the galvanometer scanning mirrors 1200 can be focused by an objective lens 1210 onto a sample on the apical side of a growth substrate insert such as a filter 1220 placed in an m x n multi-chambered plate 1230.
  • the m x n plate can be supported by an automated plate moving system 1240 which is motorized and capable of moving the multi-chambered plate in three physical dimensions 1250 such that the light focused by the objective lens 1210 can interrogate multiple samples contained in the multi-chambered plate 1230.
  • Output signals 1260 from a computer 1270 can be used to control the movement of automated plate mover 1215.
  • the computer 1270 can be used to process images according to an exemplary procedure and grade the effectiveness of each compound added to the biological sample.
  • Figure 13 shows a diagram of another high-throughput screening system which can utilize the exemplary system of Figure 1 .
  • the apodized light from the galvanometer scanning mirrors 1300 can be focused by an objective lens 1310 onto a sample on the basolateral side of a growth substrate insert, such as a filter 1320 placed in an m x n multi-chambered plate 1330.
  • the m x n plate can be support by an automated plate moving system 1340 which can be motorized and capable of moving the multi-chambered plate in three physical dimensions 1350 such that the light focused by the objective lens 1310 interrogates multiple samples contained in the multi-chambered plate 1330.
  • Output signals 1360 from a computer 1370 can be used to control the movement of automated plate mover 1315.
  • the computer 1370 can be used to process images according to an exemplary procedure and grade the effectiveness of each compound added to the biological sample.
  • Figure 14 illustrates a diagram of the exemplary system shown in Figure 12 and modified such that an additional optical path is implemented to provide fluorescence excitation light to a biological sample.
  • the additional path begins with broadband light/beam/radiation 1400 having been transmitted through the beam splitter 1405 and directed by a mirror 1410 through an excitation filter 1415 before being focused by a lens 1420 onto a single mode fiber optic patch cable 1425.
  • the light/beam/radiation transmitted by the fiber optic cable 1425 can be re-collimated by a lens 1430 and directed by dichroic mirrors 1435 and 1440 into a common optical path as the exemplary embodiment in Figure 12 .
  • the combined light can be directed by a scanning galvanometer 1450 through a focusing objective lens 1460 onto the apical side of a biological sample 1465 as in the system shown in Figure 12 .
  • the light/beam/radiation reflected by the sample can be collected by the objective lens 1460 and separated into a fluorescence path 1470 and ⁇ OCT path by dichroic mirror 1440.
  • the fluorescence light/beam/radiation can be further separated from the source light by dichroic mirror 1435 before passing through emission filters 1475 and being focused by lens 1480 onto the entrance pupil of fiber optic patch cable 1482.
  • Fluorescence light/beam/radiation transmitted by the fiber optic patch cable 1482 can be re-collimated by a lens 1484 and split into its component spectral frequencies by a diffraction grating 1486 which are then focused by a lens 1488 onto a detection array 1490.
  • Information from the detection array 1490 can be transmitted to a computer 1492 that processes the fluorescence information for display 1494 and storage 1496.
  • FIG. 15 Another configuration of a dual-modality fluorescence ⁇ OCT system is shown in Figure 15 , which illustrates an alternate exemplary configuration of the system shown in Figure 14 as an inverted imaging system (which is also a modification of the exemplary system in Figure 13 ).
  • an additional optical path can be implemented to provide fluorescence excitation light to a biological sample.
  • the additional path begins with broadband light/beam/radiation 1500 having been transmitted through the beam splitter 1505 and directed by a mirror 1510 through an excitation filter 1515 before being focused by a lens 1520 onto the entrance pupil of a single mode fiber optic patch cable 1525.
  • the light/beam/radiation transmitted by the fiber optic cable 1525 can be re-collimated by a lens 1530 and directed by dichroic mirrors 1535 and 1540 into a common optical path as the system shown in Figure 13 .
  • the combined light/beam/radiation can be directed by a scanning galvanometer 1545 through a focusing objective lens 1550 onto the basolateral side of a biological sample 1555, similarly to the system shown in Figure 13 .
  • the light/beam/radiation reflected by the sample can be collected by the objective lens 1550, and separated into a fluorescence path 1560 and ⁇ OCT path by dichroic mirror 1540.
  • the fluorescence light/beam/radiation can further be separated from the source light by dichroic mirror 1535 before passing through emission filters 1565 and being focused by lens 1570 onto the entrance pupil of fiber optic patch cable 1575.
  • Fluorescence light/beam/radiation transmitted by the fiber optic patch cable 1575 can be re-collimated by a lens 1580, and split into its component spectral frequencies by a diffraction grating 1585 which are then focused by a lens 1590 onto a detection array 1592.
  • Information from the detection array 1592 can be transmitted to a computer 1594 that processes the fluorescence information for display 1596 and storage 1598.
  • FIG. 16a A graph of exemplary results combining data from both fluorescence microscopy and ⁇ OCT in a dual-modality configuration is shown in Figure 16a .
  • An experiment was conducted on a HBE cell culture in which the unloaded cells receive a sudden impact of mucus (1600) while imaged simultaneously with ⁇ OCT and fluorescence microscopy.
  • the ⁇ OCT images were used to determine ciliary beat frequency (1610) and PCL depth reduction (1630), while intracellular calcium ion concentration is revealed by a fluorescent assay. From 1-5 seconds, the PCL height, CBF and calcium were at the basal condition. Between 6-7 sec, 10 ⁇ L of mucus acquired from a normal subject reached the epithelial surface.
  • the exemplary high-throughput screening described herein can include a computer workstation for system control and image acquisition.
  • An exemplary interface of the user control and display system is shown in Figure 17 .
  • the user can regulate the automated scanning process with a series of controls 1700.
  • the location of the scanning light/beam/radiation relative to an arbitrary home position 1710 is displayed and the user can provide manual commands with position controls 1720.
  • the progress 1730 of the automated scanning is also provided to the user.
  • Exemplary ⁇ OCT images can be displayed in one or more viewing windows 1740 in which additional information about the sample being scanned can be displayed 1750.
  • analysis can be performed on the series of images from each position to produce the metrics relevant to the evaluation of the compound under study.
  • This disclosure can include automated procedures employed to determine airway surface liquid depth, mucociliary transport rate, and ciliary beat frequency from the exemplary ⁇ OCT image data.
  • Figure 18 shows a flow diagram of a method and a procedure for an automated airway surface liquid (ASL) depth measurement.
  • the ASL depth is the distance in microns from the apical border of the cell layer to the top of the mucus secretion.
  • the first block 1800 can be to load a sequence of 20 consecutive images of the HBE cells.
  • the second block 1810 can be to create a new image which has the minimum value at each pixel over these 20 frames. This exemplary step can mitigate the possibility of transient noise and flowing microparticles incorrectly being classified as edges.
  • Steps 1820 and 1830 can perform a Laplacian of Gaussian (LoG) operation on the processed image, a standard edge detection algorithm.
  • LiG Laplacian of Gaussian
  • each axial line in the resultant LoG image is considered independently and a peak detection procedure can be applied.
  • the 5 highest unique peaks detected are labeled from top to bottom as the top of mucus layer, apical border of cell layer, top border of filter media, bottom border of filter media and bottom petri dish (block 1850).
  • the ASL depth for each axial line can be calculated as the distance between the top of mucus layer and the apical border of the cell layer via the known conversion between pixels and microns, using the approximation that mucus has the same refractive index as water.
  • the overall ASL depth can be computed as the median value across all axial lines in the image.
  • an image 1900 is an exemplary minimum intensity image over 20 frames.
  • the intensity and number of flowing microparticles in the mucus can be greatly reduced by the minimum operation.
  • An image 1910 is an exemplary result of a Laplacian of Gaussian operation.
  • the high intensity regions of this image now correspond to edges in the previous image.
  • the values of an exemplary single axial line of the Laplacian of Gaussian image are plotted, showing, e.g., 5 distinct peaks corresponding to the 5 repeatable edges in the original image.
  • the exemplary distance between the apical cell border and top of mucus peaks is measured and collated in a procedure 1930, showing a distribution of ASL depths.
  • the final exemplary ASL depth 1940 can be recorded as the median of this distribution.
  • Figure 20 illustrates a flow diagram of an exemplary method and/or procedure for automated mucociliary transport rate (MCT) measurement.
  • the image can be cropped to limit the region of interest to the mucus between these two borders.
  • the weighting function used can be a Gaussian kernel.
  • images 2110, 2120 and 2130 can demonstrate the characteristic mucus heterogeneity that allows for tracking.
  • the exemplary images 2110, 2120 and 2130 are three exemplary frames of the same image sequence of wild-type HBE cells, separated by 1 second each.
  • a section 2115 can be identified as the region of greatest variation within 2110, and can be thus chosen as the reference image.
  • Weighted cross-correlation can identify sections 2125 and 2135 as the most likely locations for reference image 2115 within the exemplary images 2120 and 2130, respectively.
  • Performing this exemplary calculation for every frame between sections 2110 and 2130 facilitates a reconstruction of the path of reference image 2110, shown in image 2140.
  • the exemplary MCT can then be extracted from this path using the known conversion from pixels to microns.
  • Figure 22 shows a flow diagram of exemplary method and/or procedure for automated ciliary beat frequency (CBF) measurement.
  • the first block 2200 is to locate the apical surface of the cell layer, utilizing the exemplary ASL procedure described herein with reference to Figure 18 .
  • This exemplary border can be used in block 2210 to crop to region of interest to, e.g., the 10 micron area immediately above the apical epithelial border, where we expect to find beating cilia.
  • an FFT can be performed on the intensity value over 4 seconds for each pixel in this region.
  • Pixels that are displaying regular ciliary motion will have distinct peaks in their FFT at the ciliary beat frequency, while pixels uninvolved with ciliary motion can have unremarkable FFTs.
  • the FFT results can be averaged over every 10 micron transverse section in this region of interest (step 2230).
  • a peak detection procedure can be applied to the resulting averaged FFT to determine whether this region has consistent ciliary motion. If no peak is found, the section can be ignored.
  • the peak frequency e.g., for all sections that have valid frequency peaks can be recorded, and the final outputted CBF can be the median of these peak frequencies (blocks 2250 and 2260).
  • image 2300 can be an exemplary initial image
  • image 2310 can be the cropped region of interest following image segmentation.
  • Sections 2320, 2330 and 2340 can be, e.g., three exemplary 10 micron transverse sections and their corresponding averaged FFTs are shown in exemplary graphs 2350, 2360 and 2370, respectively.
  • the graphs 2350 and 2370 illustrate distinct peaks at 8Hz and 8.25Hz, respectively, while there is no notable peak in graph 2360. Therefore, the sections 2320 and 2340 can be used as valid regions to determine CBF, while graph 2330 can be ignored.
  • Figure 24 shows exemplary images providing image quality control. Each exemplary automated procedure can have rejection criteria to force a repeat imaging and/or flag for manual review.
  • Illustration 2400 shows an exemplary acceptable image.
  • Illustration 2410 shows an exemplary image that has no endogenous microparticles visualized, so MCT or viscosity measurement cannot be performed. This exemplary criterion is implemented by rejecting images, where the pixel intensity variation within the mucus region is below a specified threshold.
  • Illustration 2420 can be an exemplary image of irregular cell shapes in the cell layer, indicating an issue with the cell culture. This can be detected by flagging images where the variation in the axial position of the apical cell layer is higher than a specified threshold.
  • Illustration 2430 can be an exemplary case in which the mucus layer is nonexistent or negligible as a result of cell culture error or defective cells producing highly dehydrated mucus.
  • the exemplary cases can be detected when the ASL depth is below a specified threshold.
  • Other reasons for flagging an image for manual review can include lack of repeatable ciliary motion or inability to segment the filter layer, indicating that the cell culture is not in the proper focus plane.
  • An exemplary consequence of a high-throughput system can be a generation of large amounts of data.
  • a management scheme can be provided for the copious volumes of image data and derived metrics generated by the exemplary ⁇ OCT system, as shown in a flow diagram and configuration of Figure 25 . This exemplary management approach is described as follows.
  • data is obtained from the exemplary ⁇ OCT imaging, including the use of airway surface functional microanatomy in block 2520 (which may include airway surface liquid depth, periciliary liquid depth, ciliary beat frequency, and mucociliary transport), in block 2530 properties of mucus can be determined by particle tracking microrheology, and in block 2540, indicators of cell and tissue viability can be combined with additional imaging modality data including in block 2550, data from fluorescent probe indicators and in block 2560, transepithelial voltage/resistance testing. In block 2570, these data can then be subjected to data cleaning to remove data affected by toxicity (e.g. indicators of poor cell and tissue viability) or unreliable data (e.g. data outside reasonable parameters).
  • toxicity e.g. indicators of poor cell and tissue viability
  • unreliable data e.g. data outside reasonable parameters
  • data can be prioritized and a scoring system can be provided based on the specific biological question to be addressed by the screen or secondary characterization. Examples are shown of relative priority of various ⁇ OCT parameters, and prioritization scheme is not limited to the examples shown in Figure 25 .
  • exemplary results can be calculated based on implementation of the informatics scheme, yielding final results in block 2595.
  • Another exemplary ⁇ OCT application can be used to perform rheology by the tracking of endogenous particles in mucus to determine the dynamic viscoelastic properties of the medium.
  • Figure 26 shows a diagram of an exemplary process from which dynamic viscosity can be calculated using the exemplary ⁇ OCT images.
  • section 2600 an exemplary image of cystic fibrosis mucus are provided, which are imaged using the exemplary embodiment(s) of the apparatus according to the present invention.
  • Endogenous microparticles can be seen in this exemplary image. Both endogenous and exogenous particles can be localized using a standard commercially available centroid-locating algorithm.
  • Particle position can be tracked in one, two, or three dimensions over time; full three-dimensional tracking allows the measurement of viscosity along all spatial coordinates and captures any anisotropic diffusion behavior.
  • Section 2610 shows an exemplary two-dimensional particle track taken by the highlighted particle over the image sequence.
  • the path of each particle can be a function of both the bulk motion of the mucus and the random Brownian motion of each particle.
  • the mean velocity vector of all tracked particles can be subtracted from each individual particle path to remove the effect of bulk motion, a process further illustrated in Figure 27 .
  • the mean squared displacement (MSD) over time of each particle due to Brownian motion can be calculated using this modified path. Accurate estimation of the expected MSD requires averaging the MSD of multiple particles.
  • Section 2620 shows a plot of MSD averaged over about 30 particles fit to a linear regression. For example, MSD as a function of time can be converted to dynamic viscosity using the Stokes Einstein relationship shown in section 2630. The resulting dynamic viscosity plot is shown in section 2640.
  • Figure 27 illustrates a set of graphs providing the bulk motion subtraction from an exemplary dataset, a component of the process shown in Figure 26 .
  • Graphs 2700 and 2710 are x- and y-direction displacements, respectively, of 19 particles tracked over 1.2 seconds.
  • the bulk motion can be recognizable as a drift away from 0 common to all tracks, with the mean displacement of all tracks superimposed on the plots (portions 2705 and 2715).
  • Subtraction of the mean displacement in both x and y directions yields particle tracks with the bulk motion eliminated (portions 2720 and 2730).
  • the effectiveness of bulk motion subtraction was validated by comparing the measured the MSD of natural inclusions in mucus in the absence versus presence of bulk motion.
  • Graph 2740 shows MSDs from collected mucus measured without motion, with induced motion in the axial direction, and with induced motion in the transverse direction.
  • Graph 2750 shows MSDs from epithelial mucus with no ciliary motion present and with active ciliary clearance (which causes bulk motion of the mucus layer). The equivalence of each static and in-motion mucus MSD measurements can indicate a successful removal of the bulk motion component.
  • Exemplary results from ⁇ OCT rheology in a validation test appear in exemplary graphs illustrated in Figure 28 , which show the mean squared displacement and calculated dynamic viscosity of a solution of phosphate buffer solution (PBS) with exogenous microparticles.
  • PBS phosphate buffer solution
  • Graph 2800 indicates the mean squared displacement of the aggregated tracks with a linear regression versus the calculated theoretical displacement from the known viscosity of PBS.
  • Graph 2810 indicates the resulting computed dynamic viscosity over a range of frequencies.
  • An exemplary standard method for optical particle-tracking rheology is fluorescence microscopy, which can be compared to the exemplary ⁇ OCT results as shown in Figure 29 using samples from the same expectorated sputum.
  • Traditional fluorescence exogenous particle tracking (line 2900) and the exemplary ⁇ OCT-based endogenous particle tracking (line 2910) can produce similar results, thus validating the potential of ⁇ OCT for measuring the mechanical properties of mucus.
  • Exemplary results from the exemplary ⁇ OCT rheology procedure on normal and CF sputum are shown in Figure 30 .
  • the exemplary ⁇ OCT images of normal (image 3000) and CF (image 3010) mucus indicate natural inclusions (e.g., diameter ⁇ 700 nm, yellow circles).
  • Corresponding two-dimensional trajectories are shown for normal (illustration 3020) and CF (illustration 3030).
  • Bar chart 3040 indicates MSDs of natural particles in the respective cases, and statistical significance in this 5-measurement sample is demonstrated with p ⁇ 0.05.

Landscapes

  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Optics & Photonics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Claims (6)

  1. Eine Optische Kohärenztomographievorrichtung, OCT, die in einem Organsystem innerhalb eines Atmungssystems sowohl bei Menschen als auch bei Tieren anwendbar ist, wobei die Vorrichtung ausgeführt ist, Daten bezüglich mindestens einer Probe des Atmungssystems zu erhalten, wobei die Vorrichtung umfasst:
    eine pulmonale µOCT-Sonde,
    mindestens eine Computeranordnung, die interferometrische Informationen empfängt, die auf von einer Referenz und der Probe gelieferter Strahlung beruhen,
    wobei die mindestens eine Computeranordnung ausgeführt ist zum:
    a. Erhalten dynamischer Trackingdaten in Bezug auf Partikel, die der mindestens einen Probe zugehörig sind, anhand der interferometrischen Informationen, wobei die mindestens eine Probe Schleim enthält, und die Partikel Einschlüsse in dem Schleim enthalten, und
    b. Bestimmen von biomechanischen Eigenschaften der mindestens einen Probe anhand der dynamischen Trackingdaten.
  2. Die Vorrichtung nach Anspruch 1, wobei die Partikel auch der mindestens einen Probe zugesetzte Partikel umfassen.
  3. Die Vorrichtung nach Anspruch 1, wobei die Vorrichtung ausgeführt ist, dynamische Trackingdaten in Bezug auf Einschlüsse mit einem Durchmesser von weniger als 1 Mikrometer zu erhalten.
  4. Die Vorrichtung nach Anspruch 1, wobei die Vorrichtung ausgeführt ist, dynamische Trackingdaten in Bezug auf Einschlüsse mit einem Durchmesser von weniger als 2 Mikrometer zu erhalten.
  5. Die Vorrichtung nach Anspruch 1, wobei die Vorrichtung ausgeführt ist, dynamische Trackingdaten in Bezug auf Einschlüsse mit einem Durchmesser von weniger als 5 Mikrometer zu erhalten.
  6. Die Vorrichtung nach Anspruch 1, wobei die dynamischen Trackingdaten eine Messung von mindestens einem von einer Verschiebung oder einer Größe von mindestens einem der Partikel umfassen.
EP21151195.1A 2011-08-25 2012-08-27 Vorrichtung zur bereitstellung mikrooptischer kohärenztomographie in einem atmungssystem Active EP3835718B1 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161527446P 2011-08-25 2011-08-25
US201161527701P 2011-08-26 2011-08-26
EP12826303.5A EP2748587B1 (de) 2011-08-25 2012-08-27 Verfahren und anordnungen zur bereitstellung mikrooptischer kohärenztomographieverfahren
PCT/US2012/052553 WO2013029047A1 (en) 2011-08-25 2012-08-27 Methods, systems, arrangements and computer-accessible medium for providing micro-optical coherence tomography procedures

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP12826303.5A Division EP2748587B1 (de) 2011-08-25 2012-08-27 Verfahren und anordnungen zur bereitstellung mikrooptischer kohärenztomographieverfahren

Publications (2)

Publication Number Publication Date
EP3835718A1 EP3835718A1 (de) 2021-06-16
EP3835718B1 true EP3835718B1 (de) 2023-07-26

Family

ID=47746926

Family Applications (2)

Application Number Title Priority Date Filing Date
EP21151195.1A Active EP3835718B1 (de) 2011-08-25 2012-08-27 Vorrichtung zur bereitstellung mikrooptischer kohärenztomographie in einem atmungssystem
EP12826303.5A Active EP2748587B1 (de) 2011-08-25 2012-08-27 Verfahren und anordnungen zur bereitstellung mikrooptischer kohärenztomographieverfahren

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP12826303.5A Active EP2748587B1 (de) 2011-08-25 2012-08-27 Verfahren und anordnungen zur bereitstellung mikrooptischer kohärenztomographieverfahren

Country Status (3)

Country Link
US (2) US10241028B2 (de)
EP (2) EP3835718B1 (de)
WO (1) WO2013029047A1 (de)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI708052B (zh) 2011-08-29 2020-10-21 美商安美基公司 用於非破壞性檢測-流體中未溶解粒子之方法及裝置
US9664606B2 (en) * 2012-09-17 2017-05-30 The General Hospital Corporation Compensation for causes of temporal fluctuations of backscattered speckle patterns in laser speckle rheology of biological fluids
US9431788B2 (en) * 2014-04-21 2016-08-30 Ofs Fitel, Llc Mode converter for high power, higher-order mode optical fiber amplifiers
KR102251245B1 (ko) * 2014-04-30 2021-05-12 삼성전자주식회사 관심 영역별 추가 정보 제공 장치 및 방법
AT515521B1 (de) * 2014-07-23 2015-10-15 Trumpf Maschinen Austria Gmbh Biegewinkelmessvorrichtung und Verfahren zum Messen eines Biegewinkels mittels der Biegewinkelmessvorrichtung
US20170219485A1 (en) * 2014-10-01 2017-08-03 Purdue Research Foundation Organism Identification
WO2016126879A1 (en) * 2015-02-03 2016-08-11 The Arizona Board Of Regents On Behalf Of The University Of Arizona Falloposcope and method for ovarian cancer detection
US12144642B2 (en) * 2015-02-03 2024-11-19 Arizona Board Of Regents On Behalf Of The University Of Arizona Cell-collecting falloposcope and method for ovarian cancer detection
CN105548018B (zh) * 2015-11-30 2018-11-06 临沂大学 一种固液体系中固含量的测量装置及测量方法
WO2017132745A1 (en) * 2016-02-05 2017-08-10 Synaptive Medical (Barbados) Inc. System and method for providing surgical guidance based on polarization-sensitive optical coherence tomography
US10646111B2 (en) 2016-09-23 2020-05-12 Canon U.S.A., Inc. Spectrally encoded endoscopy apparatus and methods
US20180188019A1 (en) * 2016-12-31 2018-07-05 Alcatel-Lucent Usa Inc. Hybrid Raman And Optical Coherence Tomography Imaging
GB201701691D0 (en) * 2017-02-01 2017-03-15 Illumina Inc System and method with reflective fiducials
GB201701686D0 (en) 2017-02-01 2017-03-15 Illunina Inc System & method with fiducials having offset layouts
GB201701688D0 (en) 2017-02-01 2017-03-15 Illumia Inc System and method with fiducials in non-recliner layouts
GB201701689D0 (en) 2017-02-01 2017-03-15 Illumia Inc System and method with fiducials of non-closed shapes
EP3576868A4 (de) 2017-02-01 2021-03-17 Illumina, Inc. System und verfahren mit referenzmarken entsprechend mehrerer erregungsfrequenzen
US10088660B2 (en) 2017-02-10 2018-10-02 Amgen Inc. Imaging system for counting and sizing particles in fluid-filled vessels
EP3580550B1 (de) * 2017-02-10 2024-05-22 Amgen Inc. Bildgebungssystem zum zählen und klassifizieren von partikeln in flüssigkeitsgefüllten gefässen
CA3063240A1 (en) * 2017-05-30 2018-12-06 Nanolockin Gmbh Method for characterizing particles producing heat when exposed to light and device for carrying out the method
DE102017115922C5 (de) * 2017-07-14 2023-03-23 Precitec Gmbh & Co. Kg Verfahren und Vorrichtung zur Messung und Einstellung eines Abstands zwischen einem Bearbeitungskopf und einem Werkstück sowie dazugehöriges Verfahren zur Regelung
JP7121606B2 (ja) * 2018-09-11 2022-08-18 浜松ホトニクス株式会社 光計測装置
IL282493B1 (en) * 2018-10-29 2024-11-01 Lyseonics BV A method and system for detection of electromagnetic radiation
WO2021041712A1 (en) * 2019-08-28 2021-03-04 Lundquist Institute For Biomedical Innovation At Harbor-Ucla Medical Center Optical coherence tomography based sperm detection method and devices and systems for performing the same
IL278987A (en) * 2019-12-05 2021-06-30 Continuse Biometrics Ltd System and method for passively monitoring a sample
EP3896432A1 (de) * 2020-04-15 2021-10-20 HighFly Therapeutics (HK) Limited System und verfahren zur fluoreszenzdetektion
US12076118B2 (en) 2021-10-01 2024-09-03 Canon U.S.A., Inc. Devices, systems, and methods for detecting external elastic lamina (EEL) from intravascular OCT images

Family Cites Families (524)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2339754A (en) 1941-03-04 1944-01-25 Westinghouse Electric & Mfg Co Supervisory apparatus
US3090753A (en) 1960-08-02 1963-05-21 Exxon Research Engineering Co Ester oil compositions containing acid anhydride
US3601480A (en) 1968-07-10 1971-08-24 Physics Int Co Optical tunnel high-speed camera system
JPS4932484U (de) 1972-06-19 1974-03-20
US3872407A (en) 1972-09-01 1975-03-18 Us Navy Rapidly tunable laser
JPS584481Y2 (ja) 1973-06-23 1983-01-26 オリンパス光学工業株式会社 ナイシキヨウシヤヘンカンコウガクケイ
FR2253410A5 (de) 1973-12-03 1975-06-27 Inst Nat Sante Rech Med
US3941121A (en) 1974-12-20 1976-03-02 The University Of Cincinnati Focusing fiber-optic needle endoscope
US3983507A (en) 1975-01-06 1976-09-28 Research Corporation Tunable laser systems and method
US3973219A (en) 1975-04-24 1976-08-03 Cornell Research Foundation, Inc. Very rapidly tuned cw dye laser
US4030831A (en) 1976-03-22 1977-06-21 The United States Of America As Represented By The Secretary Of The Navy Phase detector for optical figure sensing
US4141362A (en) 1977-05-23 1979-02-27 Richard Wolf Gmbh Laser endoscope
US4224929A (en) 1977-11-08 1980-09-30 Olympus Optical Co., Ltd. Endoscope with expansible cuff member and operation section
US4339954A (en) 1978-03-09 1982-07-20 National Research Development Corporation Measurement of small movements
GB2030313A (en) 1978-06-29 1980-04-02 Wolf Gmbh Richard Endoscopes
FR2448728A1 (fr) 1979-02-07 1980-09-05 Thomson Csf Dispositif joint tournant pour liaison par conducteurs optiques et systeme comportant un tel dispositif
US4295738A (en) 1979-08-30 1981-10-20 United Technologies Corporation Fiber optic strain sensor
US4300816A (en) 1979-08-30 1981-11-17 United Technologies Corporation Wide band multicore optical fiber
US4428643A (en) 1981-04-08 1984-01-31 Xerox Corporation Optical scanning system with wavelength shift correction
US5065331A (en) 1981-05-18 1991-11-12 Vachon Reginald I Apparatus and method for determining the stress and strain in pipes, pressure vessels, structural members and other deformable bodies
GB2106736B (en) 1981-09-03 1985-06-12 Standard Telephones Cables Ltd Optical transmission system
US4479499A (en) 1982-01-29 1984-10-30 Alfano Robert R Method and apparatus for detecting the presence of caries in teeth using visible light
US5302025A (en) 1982-08-06 1994-04-12 Kleinerman Marcos Y Optical systems for sensing temperature and other physical parameters
US4601036A (en) 1982-09-30 1986-07-15 Honeywell Inc. Rapidly tunable laser
HU187188B (en) 1982-11-25 1985-11-28 Koezponti Elelmiszeripari Device for generating radiation of controllable spectral structure
CH663466A5 (fr) 1983-09-12 1987-12-15 Battelle Memorial Institute Procede et dispositif pour determiner la position d'un objet par rapport a une reference.
US4639999A (en) 1984-11-02 1987-02-03 Xerox Corporation High resolution, high efficiency I.R. LED printing array fabrication method
US4763977A (en) 1985-01-09 1988-08-16 Canadian Patents And Development Limited-Societe Optical fiber coupler with tunable coupling ratio and method of making
US5318024A (en) 1985-03-22 1994-06-07 Massachusetts Institute Of Technology Laser endoscope for spectroscopic imaging
EP0590268B1 (de) 1985-03-22 1998-07-01 Massachusetts Institute Of Technology Faseroptisches Sondensystem zur spektralen Diagnose von Gewebe
DE3610165A1 (de) 1985-03-27 1986-10-02 Olympus Optical Co., Ltd., Tokio/Tokyo Optisches abtastmikroskop
US4607622A (en) 1985-04-11 1986-08-26 Charles D. Fritch Fiber optic ocular endoscope
US4631498A (en) 1985-04-26 1986-12-23 Hewlett-Packard Company CW Laser wavemeter/frequency locking technique
US4650327A (en) 1985-10-28 1987-03-17 Oximetrix, Inc. Optical catheter calibrating assembly
US5040889A (en) 1986-05-30 1991-08-20 Pacific Scientific Company Spectrometer with combined visible and ultraviolet sample illumination
CA1290019C (en) 1986-06-20 1991-10-01 Hideo Kuwahara Dual balanced optical signal receiver
US4770492A (en) 1986-10-28 1988-09-13 Spectran Corporation Pressure or strain sensitive optical fiber
JPH0824665B2 (ja) 1986-11-28 1996-03-13 オリンパス光学工業株式会社 内視鏡装置
US4744656A (en) 1986-12-08 1988-05-17 Spectramed, Inc. Disposable calibration boot for optical-type cardiovascular catheter
US4751706A (en) 1986-12-31 1988-06-14 The United States Of America As Represented By The Secretary Of The Army Laser for providing rapid sequence of different wavelengths
US4834111A (en) 1987-01-12 1989-05-30 The Trustees Of Columbia University In The City Of New York Heterodyne interferometer
CA1339426C (en) 1987-09-01 1997-09-02 Michael R. Layton Hydrophone demodulator circuit and method
US5202931A (en) 1987-10-06 1993-04-13 Cell Analysis Systems, Inc. Methods and apparatus for the quantitation of nuclear protein
US4909631A (en) 1987-12-18 1990-03-20 Tan Raul Y Method for film thickness and refractive index determination
US4890901A (en) 1987-12-22 1990-01-02 Hughes Aircraft Company Color corrector for embedded prisms
US4892406A (en) 1988-01-11 1990-01-09 United Technologies Corporation Method of and arrangement for measuring vibrations
FR2626367B1 (fr) 1988-01-25 1990-05-11 Thomson Csf Capteur de temperature multipoints a fibre optique
FR2626383B1 (fr) 1988-01-27 1991-10-25 Commissariat Energie Atomique Procede de microscopie optique confocale a balayage et en profondeur de champ etendue et dispositifs pour la mise en oeuvre du procede
US4925302A (en) 1988-04-13 1990-05-15 Hewlett-Packard Company Frequency locking device
US5730731A (en) 1988-04-28 1998-03-24 Thomas J. Fogarty Pressure-based irrigation accumulator
US4998972A (en) 1988-04-28 1991-03-12 Thomas J. Fogarty Real time angioscopy imaging system
US4905169A (en) 1988-06-02 1990-02-27 The United States Of America As Represented By The United States Department Of Energy Method and apparatus for simultaneously measuring a plurality of spectral wavelengths present in electromagnetic radiation
US5242437A (en) 1988-06-10 1993-09-07 Trimedyne Laser Systems, Inc. Medical device applying localized high intensity light and heat, particularly for destruction of the endometrium
EP0393165B2 (de) 1988-07-13 2007-07-25 Optiscan Pty Ltd Confokales abtast-endoskop
US5214538A (en) 1988-07-25 1993-05-25 Keymed (Medical And Industrial Equipment) Limited Optical apparatus
GB8817672D0 (en) 1988-07-25 1988-09-01 Sira Ltd Optical apparatus
US4868834A (en) 1988-09-14 1989-09-19 The United States Of America As Represented By The Secretary Of The Army System for rapidly tuning a low pressure pulsed laser
DE3833602A1 (de) 1988-10-03 1990-02-15 Krupp Gmbh Spektrometer zur gleichzeitigen intensitaetsmessung in verschiedenen spektralbereichen
US4940328A (en) 1988-11-04 1990-07-10 Georgia Tech Research Corporation Optical sensing apparatus and method
US4966589A (en) 1988-11-14 1990-10-30 Hemedix International, Inc. Intravenous catheter placement device
EP0449883B1 (de) 1988-12-21 1996-01-31 Massachusetts Institute Of Technology Verfahren für laserinduzierte fluoreszenz von gewebe
US5046501A (en) 1989-01-18 1991-09-10 Wayne State University Atherosclerotic identification
US5085496A (en) 1989-03-31 1992-02-04 Sharp Kabushiki Kaisha Optical element and optical pickup device comprising it
US5317389A (en) 1989-06-12 1994-05-31 California Institute Of Technology Method and apparatus for white-light dispersed-fringe interferometric measurement of corneal topography
US4965599A (en) 1989-11-13 1990-10-23 Eastman Kodak Company Scanning apparatus for halftone image screen writing
US5133035A (en) 1989-11-14 1992-07-21 Hicks John W Multifiber endoscope with multiple scanning modes to produce an image free of fixed pattern noise
US4984888A (en) 1989-12-13 1991-01-15 Imo Industries, Inc. Two-dimensional spectrometer
KR930003307B1 (ko) 1989-12-14 1993-04-24 주식회사 금성사 입체용 프로젝터
US5251009A (en) 1990-01-22 1993-10-05 Ciba-Geigy Corporation Interferometric measuring arrangement for refractive index measurements in capillary tubes
DD293205B5 (de) 1990-03-05 1995-06-29 Zeiss Carl Jena Gmbh Lichtleiterfuehrung fuer ein medizinisches Beobachtungsgeraet
US5039193A (en) 1990-04-03 1991-08-13 Focal Technologies Incorporated Fibre optic single mode rotary joint
US5262644A (en) 1990-06-29 1993-11-16 Southwest Research Institute Remote spectroscopy for raman and brillouin scattering
US5197470A (en) 1990-07-16 1993-03-30 Eastman Kodak Company Near infrared diagnostic method and instrument
GB9015793D0 (en) 1990-07-18 1990-09-05 Medical Res Council Confocal scanning optical microscope
US5127730A (en) 1990-08-10 1992-07-07 Regents Of The University Of Minnesota Multi-color laser scanning confocal imaging system
US5845639A (en) 1990-08-10 1998-12-08 Board Of Regents Of The University Of Washington Optical imaging methods
US5305759A (en) 1990-09-26 1994-04-26 Olympus Optical Co., Ltd. Examined body interior information observing apparatus by using photo-pulses controlling gains for depths
US5241364A (en) 1990-10-19 1993-08-31 Fuji Photo Film Co., Ltd. Confocal scanning type of phase contrast microscope and scanning microscope
US5250186A (en) 1990-10-23 1993-10-05 Cetus Corporation HPLC light scattering detector for biopolymers
US5202745A (en) 1990-11-07 1993-04-13 Hewlett-Packard Company Polarization independent optical coherence-domain reflectometry
US5275594A (en) 1990-11-09 1994-01-04 C. R. Bard, Inc. Angioplasty system having means for identification of atherosclerotic plaque
JP3035336B2 (ja) 1990-11-27 2000-04-24 興和株式会社 血流測定装置
US5228001A (en) 1991-01-23 1993-07-13 Syracuse University Optical random access memory
US5784162A (en) 1993-08-18 1998-07-21 Applied Spectral Imaging Ltd. Spectral bio-imaging methods for biological research, medical diagnostics and therapy
US6198532B1 (en) 1991-02-22 2001-03-06 Applied Spectral Imaging Ltd. Spectral bio-imaging of the eye
US5293872A (en) 1991-04-03 1994-03-15 Alfano Robert R Method for distinguishing between calcified atherosclerotic tissue and fibrous atherosclerotic tissue or normal cardiovascular tissue using Raman spectroscopy
US5748598A (en) 1995-12-22 1998-05-05 Massachusetts Institute Of Technology Apparatus and methods for reading multilayer storage media using short coherence length sources
US5956355A (en) 1991-04-29 1999-09-21 Massachusetts Institute Of Technology Method and apparatus for performing optical measurements using a rapidly frequency-tuned laser
US6485413B1 (en) 1991-04-29 2002-11-26 The General Hospital Corporation Methods and apparatus for forward-directed optical scanning instruments
US6134003A (en) 1991-04-29 2000-10-17 Massachusetts Institute Of Technology Method and apparatus for performing optical measurements using a fiber optic imaging guidewire, catheter or endoscope
US5465147A (en) 1991-04-29 1995-11-07 Massachusetts Institute Of Technology Method and apparatus for acquiring images using a ccd detector array and no transverse scanner
US6564087B1 (en) 1991-04-29 2003-05-13 Massachusetts Institute Of Technology Fiber optic needle probes for optical coherence tomography imaging
DE69227902T3 (de) 1991-04-29 2010-04-22 Massachusetts Institute Of Technology, Cambridge Vorrichtung für optische abbildung und messung
US6501551B1 (en) 1991-04-29 2002-12-31 Massachusetts Institute Of Technology Fiber optic imaging endoscope interferometer with at least one faraday rotator
US6111645A (en) 1991-04-29 2000-08-29 Massachusetts Institute Of Technology Grating based phase control optical delay line
US5441053A (en) 1991-05-03 1995-08-15 University Of Kentucky Research Foundation Apparatus and method for multiple wavelength of tissue
US5281811A (en) 1991-06-17 1994-01-25 Litton Systems, Inc. Digital wavelength division multiplex optical transducer having an improved decoder
US5208651A (en) 1991-07-16 1993-05-04 The Regents Of The University Of California Apparatus and method for measuring fluorescence intensities at a plurality of wavelengths and lifetimes
WO1993003672A1 (en) 1991-08-20 1993-03-04 Redd Douglas C B Optical histochemical analysis, in vivo detection and real-time guidance for ablation of abnormal tissues using a raman spectroscopic detection system
DE4128744C1 (de) 1991-08-29 1993-04-22 Siemens Ag, 8000 Muenchen, De
ATE150573T1 (de) 1991-12-30 1997-04-15 Philips Electronics Nv Optische einrichtung und mit einer solchen optischen einrichtung versehenes gerät zum abtasten einer informationsebene
US5353790A (en) 1992-01-17 1994-10-11 Board Of Regents, The University Of Texas System Method and apparatus for optical measurement of bilirubin in tissue
US5212667A (en) 1992-02-03 1993-05-18 General Electric Company Light imaging in a scattering medium, using ultrasonic probing and speckle image differencing
US5217456A (en) 1992-02-24 1993-06-08 Pdt Cardiovascular, Inc. Device and method for intra-vascular optical radial imaging
US5283795A (en) 1992-04-21 1994-02-01 Hughes Aircraft Company Diffraction grating driven linear frequency chirped laser
US5248876A (en) 1992-04-21 1993-09-28 International Business Machines Corporation Tandem linear scanning confocal imaging system with focal volumes at different heights
US5486701A (en) 1992-06-16 1996-01-23 Prometrix Corporation Method and apparatus for measuring reflectance in two wavelength bands to enable determination of thin film thickness
US5716324A (en) 1992-08-25 1998-02-10 Fuji Photo Film Co., Ltd. Endoscope with surface and deep portion imaging systems
US5348003A (en) 1992-09-03 1994-09-20 Sirraya, Inc. Method and apparatus for chemical analysis
US5772597A (en) 1992-09-14 1998-06-30 Sextant Medical Corporation Surgical tool end effector
US5698397A (en) 1995-06-07 1997-12-16 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
US5383467A (en) 1992-11-18 1995-01-24 Spectrascience, Inc. Guidewire catheter and apparatus for diagnostic imaging
WO1994012095A2 (en) 1992-11-18 1994-06-09 Spectrascience, Inc. Apparatus for diagnostic imaging
JPH06222242A (ja) 1993-01-27 1994-08-12 Shin Etsu Chem Co Ltd 光ファイバカプラおよびその製造方法
US5987346A (en) 1993-02-26 1999-11-16 Benaron; David A. Device and method for classification of tissue
JP3112595B2 (ja) 1993-03-17 2000-11-27 安藤電気株式会社 光周波数シフタを用いる光ファイバ歪位置測定装置
FI93781C (fi) 1993-03-18 1995-05-26 Wallac Oy Biospesifinen multiparametrinen määritysmenetelmä
DE4309056B4 (de) 1993-03-20 2006-05-24 Häusler, Gerd, Prof. Dr. Verfahren und Vorrichtung zur Ermittlung der Entfernung und Streuintensität von streuenden Punkten
DE4310209C2 (de) 1993-03-29 1996-05-30 Bruker Medizintech Optische stationäre Bildgebung in stark streuenden Medien
US5485079A (en) 1993-03-29 1996-01-16 Matsushita Electric Industrial Co., Ltd. Magneto-optical element and optical magnetic field sensor
DE4314189C1 (de) 1993-04-30 1994-11-03 Bodenseewerk Geraetetech Vorrichtung zur Untersuchung von Lichtleitfasern aus Glas mittels Heterodyn-Brillouin-Spektroskopie
US5424827A (en) 1993-04-30 1995-06-13 Litton Systems, Inc. Optical system and method for eliminating overlap of diffraction spectra
SE501932C2 (sv) 1993-04-30 1995-06-26 Ericsson Telefon Ab L M Anordning och förfarande för dispersionskompensering i ett fiberoptiskt transmissionssystem
US5454807A (en) 1993-05-14 1995-10-03 Boston Scientific Corporation Medical treatment of deeply seated tissue using optical radiation
EP0627643B1 (de) 1993-06-03 1999-05-06 Hamamatsu Photonics K.K. Optisches Laser-Abtastsystem mit Axikon
JP3234353B2 (ja) 1993-06-15 2001-12-04 富士写真フイルム株式会社 断層情報読取装置
US5803082A (en) 1993-11-09 1998-09-08 Staplevision Inc. Omnispectramammography
US5983125A (en) 1993-12-13 1999-11-09 The Research Foundation Of City College Of New York Method and apparatus for in vivo examination of subcutaneous tissues inside an organ of a body using optical spectroscopy
US5450203A (en) 1993-12-22 1995-09-12 Electroglas, Inc. Method and apparatus for determining an objects position, topography and for imaging
US5411016A (en) 1994-02-22 1995-05-02 Scimed Life Systems, Inc. Intravascular balloon catheter for use in combination with an angioscope
US5590660A (en) 1994-03-28 1997-01-07 Xillix Technologies Corp. Apparatus and method for imaging diseased tissue using integrated autofluorescence
DE4411017C2 (de) 1994-03-30 1995-06-08 Alexander Dr Knuettel Optische stationäre spektroskopische Bildgebung in stark streuenden Objekten durch spezielle Lichtfokussierung und Signal-Detektion von Licht unterschiedlicher Wellenlängen
TW275570B (de) 1994-05-05 1996-05-11 Boehringer Mannheim Gmbh
US5459325A (en) 1994-07-19 1995-10-17 Molecular Dynamics, Inc. High-speed fluorescence scanner
US6159445A (en) 1994-07-20 2000-12-12 Nycomed Imaging As Light imaging contrast agents
EP1231496B1 (de) 1994-08-18 2004-12-29 Carl Zeiss AG Mit optischer Kohärenz-Tomographie gesteuerter chirurgischer Apparat
US5491524A (en) 1994-10-05 1996-02-13 Carl Zeiss, Inc. Optical coherence tomography corneal mapping apparatus
US5740808A (en) 1996-10-28 1998-04-21 Ep Technologies, Inc Systems and methods for guilding diagnostic or therapeutic devices in interior tissue regions
US5817144A (en) 1994-10-25 1998-10-06 Latis, Inc. Method for contemporaneous application OF laser energy and localized pharmacologic therapy
US6033721A (en) 1994-10-26 2000-03-07 Revise, Inc. Image-based three-axis positioner for laser direct write microchemical reaction
US5566267A (en) 1994-12-15 1996-10-15 Ceram Optec Industries Inc. Flat surfaced optical fibers and diode laser medical delivery devices
US5600486A (en) 1995-01-30 1997-02-04 Lockheed Missiles And Space Company, Inc. Color separation microlens
US5648848A (en) 1995-02-01 1997-07-15 Nikon Precision, Inc. Beam delivery apparatus and method for interferometry using rotatable polarization chucks
DE19506484C2 (de) 1995-02-24 1999-09-16 Stiftung Fuer Lasertechnologie Verfahren und Vorrichtung zur selektiven nichtinvasiven Lasermyographie (LMG)
RU2100787C1 (ru) 1995-03-01 1997-12-27 Геликонов Валентин Михайлович Оптоволоконный интерферометр и оптоволоконный пьезоэлектрический преобразователь
WO1996028212A1 (en) 1995-03-09 1996-09-19 Innotech Usa, Inc. Laser surgical device and method of its use
US5526338A (en) 1995-03-10 1996-06-11 Yeda Research & Development Co. Ltd. Method and apparatus for storage and retrieval with multilayer optical disks
US5697373A (en) 1995-03-14 1997-12-16 Board Of Regents, The University Of Texas System Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies
US5735276A (en) 1995-03-21 1998-04-07 Lemelson; Jerome Method and apparatus for scanning and evaluating matter
US5926592A (en) 1995-03-24 1999-07-20 Optiscan Pty Ltd Optical fibre confocal imager with variable near-confocal control
US5565983A (en) 1995-05-26 1996-10-15 The Perkin-Elmer Corporation Optical spectrometer for detecting spectra in separate ranges
US5785651A (en) 1995-06-07 1998-07-28 Keravision, Inc. Distance measuring confocal microscope
US5621830A (en) 1995-06-07 1997-04-15 Smith & Nephew Dyonics Inc. Rotatable fiber optic joint
WO1997001167A1 (en) 1995-06-21 1997-01-09 Massachusetts Institute Of Technology Apparatus and method for accessing data on multilayered optical media
ATA107495A (de) 1995-06-23 1996-06-15 Fercher Adolf Friedrich Dr Kohärenz-biometrie und -tomographie mit dynamischem kohärentem fokus
CN1200174A (zh) 1995-08-24 1998-11-25 普渡研究基金会 基于荧光寿命的人体组织及其它无规则介质成象技术和光谱技术
US6016197A (en) 1995-08-25 2000-01-18 Ceramoptec Industries Inc. Compact, all-optical spectrum analyzer for chemical and biological fiber optic sensors
FR2738343B1 (fr) 1995-08-30 1997-10-24 Cohen Sabban Joseph Dispositif de microstratigraphie optique
US6763261B2 (en) 1995-09-20 2004-07-13 Board Of Regents, The University Of Texas System Method and apparatus for detecting vulnerable atherosclerotic plaque
AU709432B2 (en) 1995-09-20 1999-08-26 California Institute Of Technology Detecting thermal discrepancies in vessel walls
US6615071B1 (en) 1995-09-20 2003-09-02 Board Of Regents, The University Of Texas System Method and apparatus for detecting vulnerable atherosclerotic plaque
DE19542955C2 (de) 1995-11-17 1999-02-18 Schwind Gmbh & Co Kg Herbert Endoskop
US5719399A (en) 1995-12-18 1998-02-17 The Research Foundation Of City College Of New York Imaging and characterization of tissue based upon the preservation of polarized light transmitted therethrough
JP3699761B2 (ja) 1995-12-26 2005-09-28 オリンパス株式会社 落射蛍光顕微鏡
US5748318A (en) 1996-01-23 1998-05-05 Brown University Research Foundation Optical stress generator and detector
US5840023A (en) 1996-01-31 1998-11-24 Oraevsky; Alexander A. Optoacoustic imaging for medical diagnosis
US5642194A (en) 1996-02-05 1997-06-24 The Regents Of The University Of California White light velocity interferometer
US5862273A (en) 1996-02-23 1999-01-19 Kaiser Optical Systems, Inc. Fiber optic probe with integral optical filtering
US5843000A (en) 1996-05-07 1998-12-01 The General Hospital Corporation Optical biopsy forceps and method of diagnosing tissue
ATA84696A (de) 1996-05-14 1998-03-15 Adolf Friedrich Dr Fercher Verfahren und anordnungen zur kontrastanhebung in der optischen kohärenztomographie
US6020963A (en) 1996-06-04 2000-02-01 Northeastern University Optical quadrature Interferometer
US5795295A (en) 1996-06-25 1998-08-18 Carl Zeiss, Inc. OCT-assisted surgical microscope with multi-coordinate manipulator
US5842995A (en) 1996-06-28 1998-12-01 Board Of Regents, The Univerisity Of Texas System Spectroscopic probe for in vivo measurement of raman signals
US6245026B1 (en) 1996-07-29 2001-06-12 Farallon Medsystems, Inc. Thermography catheter
US5840075A (en) 1996-08-23 1998-11-24 Eclipse Surgical Technologies, Inc. Dual laser device for transmyocardial revascularization procedures
US6396941B1 (en) 1996-08-23 2002-05-28 Bacus Research Laboratories, Inc. Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
US6544193B2 (en) 1996-09-04 2003-04-08 Marcio Marc Abreu Noninvasive measurement of chemical substances
JPH1090603A (ja) 1996-09-18 1998-04-10 Olympus Optical Co Ltd 内視鏡光学系
US5801831A (en) 1996-09-20 1998-09-01 Institute For Space And Terrestrial Science Fabry-Perot spectrometer for detecting a spatially varying spectral signature of an extended source
WO1998013715A1 (fr) 1996-09-27 1998-04-02 Vincent Lauer Microscope generant une representation tridimensionnelle d'un objet
DE19640495C2 (de) 1996-10-01 1999-12-16 Leica Microsystems Vorrichtung zur konfokalen Oberflächenvermessung
US5843052A (en) 1996-10-04 1998-12-01 Benja-Athon; Anuthep Irrigation kit for application of fluids and chemicals for cleansing and sterilizing wounds
US5752518A (en) 1996-10-28 1998-05-19 Ep Technologies, Inc. Systems and methods for visualizing interior regions of the body
US6044288A (en) 1996-11-08 2000-03-28 Imaging Diagnostics Systems, Inc. Apparatus and method for determining the perimeter of the surface of an object being scanned
US5872879A (en) 1996-11-25 1999-02-16 Boston Scientific Corporation Rotatable connecting optical fibers
US6517532B1 (en) 1997-05-15 2003-02-11 Palomar Medical Technologies, Inc. Light energy delivery head
US6437867B2 (en) 1996-12-04 2002-08-20 The Research Foundation Of The City University Of New York Performing selected optical measurements with optical coherence domain reflectometry
US6249630B1 (en) 1996-12-13 2001-06-19 Imra America, Inc. Apparatus and method for delivery of dispersion-compensated ultrashort optical pulses with high peak power
US5871449A (en) 1996-12-27 1999-02-16 Brown; David Lloyd Device and method for locating inflamed plaque in an artery
US5991697A (en) 1996-12-31 1999-11-23 The Regents Of The University Of California Method and apparatus for optical Doppler tomographic imaging of fluid flow velocity in highly scattering media
US5760901A (en) 1997-01-28 1998-06-02 Zetetic Institute Method and apparatus for confocal interference microscopy with background amplitude reduction and compensation
US5801826A (en) 1997-02-18 1998-09-01 Williams Family Trust B Spectrometric device and method for recognizing atomic and molecular signatures
US5836877A (en) 1997-02-24 1998-11-17 Lucid Inc System for facilitating pathological examination of a lesion in tissue
US5968064A (en) 1997-02-28 1999-10-19 Lumend, Inc. Catheter system for treating a vascular occlusion
US6120516A (en) 1997-02-28 2000-09-19 Lumend, Inc. Method for treating vascular occlusion
US6010449A (en) 1997-02-28 2000-01-04 Lumend, Inc. Intravascular catheter system for treating a vascular occlusion
JP2001515382A (ja) 1997-03-06 2001-09-18 マサチューセッツ インスティチュート オブ テクノロジー 生体組織の光学走査用機器
US6201989B1 (en) 1997-03-13 2001-03-13 Biomax Technologies Inc. Methods and apparatus for detecting the rejection of transplanted tissue
US6078047A (en) 1997-03-14 2000-06-20 Lucent Technologies Inc. Method and apparatus for terahertz tomographic imaging
US5994690A (en) 1997-03-17 1999-11-30 Kulkarni; Manish D. Image enhancement in optical coherence tomography using deconvolution
GB9707414D0 (en) 1997-04-11 1997-05-28 Imperial College Anatomical probe
WO1998048838A1 (en) 1997-04-29 1998-11-05 Nycomed Imaging As Compounds
JP2001526650A (ja) 1997-04-29 2001-12-18 ニユコメド・イメージング・アクシエセルカペト 光画像造影剤
US6117128A (en) 1997-04-30 2000-09-12 Kenton W. Gregory Energy delivery catheter and method for the use thereof
US5887009A (en) 1997-05-22 1999-03-23 Optical Biopsy Technologies, Inc. Confocal optical scanning system employing a fiber laser
US6002480A (en) 1997-06-02 1999-12-14 Izatt; Joseph A. Depth-resolved spectroscopic optical coherence tomography
AU7711498A (en) 1997-06-02 1998-12-21 Joseph A. Izatt Doppler flow imaging using optical coherence tomography
US6208415B1 (en) 1997-06-12 2001-03-27 The Regents Of The University Of California Birefringence imaging in biological tissue using polarization sensitive optical coherent tomography
US5920390A (en) 1997-06-26 1999-07-06 University Of North Carolina Fiberoptic interferometer and associated method for analyzing tissue
US6048349A (en) 1997-07-09 2000-04-11 Intraluminal Therapeutics, Inc. Systems and methods for guiding a medical instrument through a body
US6058352A (en) 1997-07-25 2000-05-02 Physical Optics Corporation Accurate tissue injury assessment using hybrid neural network analysis
US5921926A (en) 1997-07-28 1999-07-13 University Of Central Florida Three dimensional optical imaging colposcopy
US5892583A (en) 1997-08-21 1999-04-06 Li; Ming-Chiang High speed inspection of a sample using superbroad radiation coherent interferometer
US6014214A (en) 1997-08-21 2000-01-11 Li; Ming-Chiang High speed inspection of a sample using coherence processing of scattered superbroad radiation
US6069698A (en) 1997-08-28 2000-05-30 Olympus Optical Co., Ltd. Optical imaging apparatus which radiates a low coherence light beam onto a test object, receives optical information from light scattered by the object, and constructs therefrom a cross-sectional image of the object
US6297018B1 (en) 1998-04-17 2001-10-02 Ljl Biosystems, Inc. Methods and apparatus for detecting nucleic acid polymorphisms
US5920373A (en) 1997-09-24 1999-07-06 Heidelberg Engineering Optische Messysteme Gmbh Method and apparatus for determining optical characteristics of a cornea
US6193676B1 (en) 1997-10-03 2001-02-27 Intraluminal Therapeutics, Inc. Guide wire assembly
US5951482A (en) 1997-10-03 1999-09-14 Intraluminal Therapeutics, Inc. Assemblies and methods for advancing a guide wire through body tissue
US6091984A (en) 1997-10-10 2000-07-18 Massachusetts Institute Of Technology Measuring tissue morphology
US5955737A (en) 1997-10-27 1999-09-21 Systems & Processes Engineering Corporation Chemometric analysis for extraction of individual fluorescence spectrum and lifetimes from a target mixture
US6134010A (en) 1997-11-07 2000-10-17 Lucid, Inc. Imaging system using polarization effects to enhance image quality
US6037579A (en) 1997-11-13 2000-03-14 Biophotonics Information Laboratories, Ltd. Optical interferometer employing multiple detectors to detect spatially distorted wavefront in imaging of scattering media
US6107048A (en) 1997-11-20 2000-08-22 Medical College Of Georgia Research Institute, Inc. Method of detecting and grading dysplasia in epithelial tissue
JP4662622B2 (ja) 1998-01-28 2011-03-30 イマージョン メディカル，インコーポレイティド 医療処置シミュレーションシステムに器械をインタフェース接続するためのインタフェース装置及び方法
US6165170A (en) 1998-01-29 2000-12-26 International Business Machines Corporation Laser dermablator and dermablation
US6048742A (en) 1998-02-26 2000-04-11 The United States Of America As Represented By The Secretary Of The Air Force Process for measuring the thickness and composition of thin semiconductor films deposited on semiconductor wafers
US6831781B2 (en) 1998-02-26 2004-12-14 The General Hospital Corporation Confocal microscopy with multi-spectral encoding and system and apparatus for spectroscopically encoded confocal microscopy
US6134033A (en) 1998-02-26 2000-10-17 Tyco Submarine Systems Ltd. Method and apparatus for improving spectral efficiency in wavelength division multiplexed transmission systems
EP2267506A3 (de) 1998-02-26 2011-03-02 The General Hospital Corporation Konfokale Mikroskopie mit multispektraler Kodierung
US6174291B1 (en) 1998-03-09 2001-01-16 Spectrascience, Inc. Optical biopsy system and methods for tissue diagnosis
US6066102A (en) 1998-03-09 2000-05-23 Spectrascience, Inc. Optical biopsy forceps system and method of diagnosing tissue
US6151522A (en) 1998-03-16 2000-11-21 The Research Foundation Of Cuny Method and system for examining biological materials using low power CW excitation raman spectroscopy
US6384915B1 (en) 1998-03-30 2002-05-07 The Regents Of The University Of California Catheter guided by optical coherence domain reflectometry
US6175669B1 (en) 1998-03-30 2001-01-16 The Regents Of The Universtiy Of California Optical coherence domain reflectometry guidewire
DE19814057B4 (de) 1998-03-30 2009-01-02 Carl Zeiss Meditec Ag Anordnung zur optischen Kohärenztomographie und Kohärenztopographie
WO1999057507A1 (en) 1998-05-01 1999-11-11 Board Of Regents, The University Of Texas System Method and apparatus for subsurface imaging
US6996549B2 (en) 1998-05-01 2006-02-07 Health Discovery Corporation Computer-aided image analysis
JPH11326826A (ja) 1998-05-13 1999-11-26 Sony Corp 照明方法及び照明装置
US6053613A (en) 1998-05-15 2000-04-25 Carl Zeiss, Inc. Optical coherence tomography with new interferometer
US5995223A (en) 1998-06-01 1999-11-30 Power; Joan Fleurette Apparatus for rapid phase imaging interferometry and method therefor
JPH11352409A (ja) 1998-06-05 1999-12-24 Olympus Optical Co Ltd 蛍光検出装置
US6549801B1 (en) 1998-06-11 2003-04-15 The Regents Of The University Of California Phase-resolved optical coherence tomography and optical doppler tomography for imaging fluid flow in tissue with fast scanning speed and high velocity sensitivity
WO2000003651A1 (en) 1998-07-15 2000-01-27 Corazon Technologies, Inc. Methods and devices for reducing the mineral content of vascular calcified lesions
US6166373A (en) 1998-07-21 2000-12-26 The Institute For Technology Development Focal plane scanner with reciprocating spatial window
WO2000019889A1 (en) 1998-10-08 2000-04-13 University Of Kentucky Research Foundation Methods and apparatus for in vivo identification and characterization of vulnerable atherosclerotic plaques
US6274871B1 (en) 1998-10-22 2001-08-14 Vysis, Inc. Method and system for performing infrared study on a biological sample
US6324419B1 (en) 1998-10-27 2001-11-27 Nejat Guzelsu Apparatus and method for non-invasive measurement of stretch
US6516014B1 (en) 1998-11-13 2003-02-04 The Research And Development Institute, Inc. Programmable frequency reference for laser frequency stabilization, and arbitrary optical clock generator, using persistent spectral hole burning
DE69932485T2 (de) 1998-11-20 2007-01-11 Fuji Photo Film Co. Ltd., Minamiashigara Blutgefäss Bilddarstellungssystem
US5975697A (en) 1998-11-25 1999-11-02 Oti Ophthalmic Technologies, Inc. Optical mapping apparatus with adjustable depth resolution
US6352502B1 (en) 1998-12-03 2002-03-05 Lightouch Medical, Inc. Methods for obtaining enhanced spectroscopic information from living tissue, noninvasive assessment of skin condition and detection of skin abnormalities
US6191862B1 (en) 1999-01-20 2001-02-20 Lightlab Imaging, Llc Methods and apparatus for high speed longitudinal scanning in imaging systems
US6272376B1 (en) 1999-01-22 2001-08-07 Cedars-Sinai Medical Center Time-resolved, laser-induced fluorescence for the characterization of organic material
US6445944B1 (en) 1999-02-01 2002-09-03 Scimed Life Systems Medical scanning system and related method of scanning
US6615072B1 (en) 1999-02-04 2003-09-02 Olympus Optical Co., Ltd. Optical imaging device
US6185271B1 (en) 1999-02-16 2001-02-06 Richard Estyn Kinsinger Helical computed tomography with feedback scan control
DE19908883A1 (de) 1999-03-02 2000-09-07 Rainer Heintzmann Verfahren zur Erhöhung der Auflösung optischer Abbildung
US6263133B1 (en) 1999-03-29 2001-07-17 Scimed Life Systems, Inc. Optical focusing, collimating and coupling systems for use with single mode optical fiber
US6859275B2 (en) 1999-04-09 2005-02-22 Plain Sight Systems, Inc. System and method for encoded spatio-spectral information processing
US6264610B1 (en) 1999-05-05 2001-07-24 The University Of Connecticut Combined ultrasound and near infrared diffused light imaging system
US6353693B1 (en) 1999-05-31 2002-03-05 Sanyo Electric Co., Ltd. Optical communication device and slip ring unit for an electronic component-mounting apparatus
US6993170B2 (en) 1999-06-23 2006-01-31 Icoria, Inc. Method for quantitative analysis of blood vessel structure
US6611833B1 (en) 1999-06-23 2003-08-26 Tissueinformatics, Inc. Methods for profiling and classifying tissue using a database that includes indices representative of a tissue population
US6208887B1 (en) 1999-06-24 2001-03-27 Richard H. Clarke Catheter-delivered low resolution Raman scattering analyzing system for detecting lesions
US7426409B2 (en) 1999-06-25 2008-09-16 Board Of Regents, The University Of Texas System Method and apparatus for detecting vulnerable atherosclerotic plaque
GB9915082D0 (en) 1999-06-28 1999-08-25 Univ London Optical fibre probe
US6359692B1 (en) 1999-07-09 2002-03-19 Zygo Corporation Method and system for profiling objects having multiple reflective surfaces using wavelength-tuning phase-shifting interferometry
JP4624618B2 (ja) 1999-07-30 2011-02-02 ボストン サイエンティフィック リミテッド カテーテル組立体の回転・並進駆動カップリング
WO2001008579A1 (en) 1999-07-30 2001-02-08 Ceramoptec Industries, Inc. Dual wavelength medical diode laser system
JP2001046321A (ja) 1999-08-09 2001-02-20 Asahi Optical Co Ltd 内視鏡装置
US6445939B1 (en) 1999-08-09 2002-09-03 Lightlab Imaging, Llc Ultra-small optical probes, imaging optics, and methods for using same
JP3869589B2 (ja) 1999-09-02 2007-01-17 ペンタックス株式会社 ファイババンドル及び内視鏡装置
US6687010B1 (en) 1999-09-09 2004-02-03 Olympus Corporation Rapid depth scanning optical imaging device
US6198956B1 (en) 1999-09-30 2001-03-06 Oti Ophthalmic Technologies Inc. High speed sector scanning apparatus having digital electronic control
US6393312B1 (en) 1999-10-13 2002-05-21 C. R. Bard, Inc. Connector for coupling an optical fiber tissue localization device to a light source
US6308092B1 (en) 1999-10-13 2001-10-23 C. R. Bard Inc. Optical fiber tissue localization device
AU1182401A (en) 1999-10-15 2001-04-23 Cellavision Ab Microscope and method for manufacturing a composite image with a high resolution
US6538817B1 (en) 1999-10-25 2003-03-25 Aculight Corporation Method and apparatus for optical coherence tomography with a multispectral laser source
JP2001125009A (ja) 1999-10-28 2001-05-11 Asahi Optical Co Ltd 内視鏡装置
WO2001036948A1 (en) 1999-11-19 2001-05-25 Jobin Yvon, Inc. Compact spectrofluorometer
DE50005933D1 (de) 1999-11-24 2004-05-06 Haag Streit Ag Koeniz Verfahren und vorrichtung zur messung optischer eigenschaften wenigstens zweier voneinander distanzierter bereiche in einem transparenten und/oder diffusiven gegenstand
US7236637B2 (en) 1999-11-24 2007-06-26 Ge Medical Systems Information Technologies, Inc. Method and apparatus for transmission and display of a compressed digitized image
US6738144B1 (en) 1999-12-17 2004-05-18 University Of Central Florida Non-invasive method and low-coherence apparatus system analysis and process control
US6680780B1 (en) 1999-12-23 2004-01-20 Agere Systems, Inc. Interferometric probe stabilization relative to subject movement
US6445485B1 (en) 2000-01-21 2002-09-03 At&T Corp. Micro-machine polarization-state controller
WO2001054580A1 (en) 2000-01-27 2001-08-02 National Research Council Of Canada Visible-near infrared spectroscopy in burn injury assessment
US6475210B1 (en) 2000-02-11 2002-11-05 Medventure Technology Corp Light treatment of vulnerable atherosclerosis plaque
US6556305B1 (en) 2000-02-17 2003-04-29 Veeco Instruments, Inc. Pulsed source scanning interferometer
US6618143B2 (en) 2000-02-18 2003-09-09 Idexx Laboratories, Inc. High numerical aperture flow cytometer and method of using same
US6751490B2 (en) 2000-03-01 2004-06-15 The Board Of Regents Of The University Of Texas System Continuous optoacoustic monitoring of hemoglobin concentration and hematocrit
US6593101B2 (en) 2000-03-28 2003-07-15 Board Of Regents, The University Of Texas System Enhancing contrast in biological imaging
US6687013B2 (en) 2000-03-28 2004-02-03 Hitachi, Ltd. Laser interferometer displacement measuring system, exposure apparatus, and electron beam lithography apparatus
US6567585B2 (en) 2000-04-04 2003-05-20 Optiscan Pty Ltd Z sharpening for fibre confocal microscopes
US6692430B2 (en) 2000-04-10 2004-02-17 C2Cure Inc. Intra vascular imaging apparatus
AU2001259188A1 (en) 2000-04-27 2001-11-07 Iridex Corporation Method and apparatus for real-time detection, control and recording of sub-clinical therapeutic laser lesions during ocular laser photocoagulation
WO2001082786A2 (en) 2000-05-03 2001-11-08 Flock Stephen T Optical imaging of subsurface anatomical structures and biomolecules
US6301048B1 (en) 2000-05-19 2001-10-09 Avanex Corporation Tunable chromatic dispersion and dispersion slope compensator utilizing a virtually imaged phased array
US6441959B1 (en) 2000-05-19 2002-08-27 Avanex Corporation Method and system for testing a tunable chromatic dispersion, dispersion slope, and polarization mode dispersion compensator utilizing a virtually imaged phased array
US6560259B1 (en) 2000-05-31 2003-05-06 Applied Optoelectronics, Inc. Spatially coherent surface-emitting, grating coupled quantum cascade laser with unstable resonance cavity
JP4460117B2 (ja) 2000-06-29 2010-05-12 独立行政法人理化学研究所 グリズム
US6757467B1 (en) 2000-07-25 2004-06-29 Optical Air Data Systems, Lp Optical fiber system
US6441356B1 (en) 2000-07-28 2002-08-27 Optical Biopsy Technologies Fiber-coupled, high-speed, angled-dual-axis optical coherence scanning microscopes
US6882432B2 (en) 2000-08-08 2005-04-19 Zygo Corporation Frequency transform phase shifting interferometry
US6972894B2 (en) 2000-08-11 2005-12-06 Crystal Fibre A/S Optical wavelength converter
US7625335B2 (en) 2000-08-25 2009-12-01 3Shape Aps Method and apparatus for three-dimensional optical scanning of interior surfaces
DE10042840A1 (de) 2000-08-30 2002-03-14 Leica Microsystems Vorrichtung und Verfahren zur Anregung von Fluoreszenzmikroskopmarkern bei der Mehrphotonen-Rastermikroskopie
WO2002021170A1 (en) 2000-09-05 2002-03-14 Arroyo Optics, Inc. System and method for fabricating components of precise optical path length
EP1434522B1 (de) 2000-10-30 2010-01-13 The General Hospital Corporation Optische systeme zur gewebeanalyse
WO2002037075A2 (en) 2000-10-31 2002-05-10 Forskningscenter Risø Optical amplification in coherent optical frequency modulated continuous wave reflectometry
JP3842101B2 (ja) 2000-10-31 2006-11-08 富士写真フイルム株式会社 内視鏡装置
US6687036B2 (en) 2000-11-03 2004-02-03 Nuonics, Inc. Multiplexed optical scanner technology
US9295391B1 (en) 2000-11-10 2016-03-29 The General Hospital Corporation Spectrally encoded miniature endoscopic imaging probe
US20040072200A1 (en) 2000-11-13 2004-04-15 Rudolf Rigler Detection of nucleic acid polymorphisms
US6665075B2 (en) 2000-11-14 2003-12-16 Wm. Marshurice University Interferometric imaging system and method
DE10057539B4 (de) 2000-11-20 2008-06-12 Robert Bosch Gmbh Interferometrische Messvorrichtung
US6558324B1 (en) 2000-11-22 2003-05-06 Siemens Medical Solutions, Inc., Usa System and method for strain image display
US6856712B2 (en) 2000-11-27 2005-02-15 University Of Washington Micro-fabricated optical waveguide for use in scanning fiber displays and scanned fiber image acquisition
US7027633B2 (en) 2000-11-30 2006-04-11 Foran David J Collaborative diagnostic systems
JP4786027B2 (ja) 2000-12-08 2011-10-05 オリンパス株式会社 光学系及び光学装置
US6501878B2 (en) 2000-12-14 2002-12-31 Nortel Networks Limited Optical fiber termination
US6687007B1 (en) 2000-12-14 2004-02-03 Kestrel Corporation Common path interferometer for spectral image generation
US6515752B2 (en) 2000-12-28 2003-02-04 Coretek, Inc. Wavelength monitoring system
US7230708B2 (en) 2000-12-28 2007-06-12 Dmitri Olegovich Lapotko Method and device for photothermal examination of microinhomogeneities
CN1239131C (zh) 2000-12-28 2006-02-01 帕洛玛医疗技术有限公司 用于皮肤的emr治疗处理的方法和装置
EP1221581A1 (de) 2001-01-04 2002-07-10 Universität Stuttgart Interferometer
US7285091B2 (en) 2001-01-11 2007-10-23 The Johns Hopkins University Assessment of tooth structure using laser based ultrasonics
US7177491B2 (en) 2001-01-12 2007-02-13 Board Of Regents The University Of Texas System Fiber-based optical low coherence tomography
US6697652B2 (en) 2001-01-19 2004-02-24 Massachusetts Institute Of Technology Fluorescence, reflectance and light scattering spectroscopy for measuring tissue
WO2002075242A2 (en) 2001-01-22 2002-09-26 Roth Jonathan E Method and apparatus for polarization-sensitive optical coherence tomography
US20020140942A1 (en) 2001-02-17 2002-10-03 Fee Michale Sean Acousto-optic monitoring and imaging in a depth sensitive manner
US6654127B2 (en) 2001-03-01 2003-11-25 Carl Zeiss Ophthalmic Systems, Inc. Optical delay line
US6721094B1 (en) 2001-03-05 2004-04-13 Sandia Corporation Long working distance interference microscope
IL142773A (en) 2001-03-08 2007-10-31 Xtellus Inc Fiber optic damper
US6563995B2 (en) 2001-04-02 2003-05-13 Lightwave Electronics Optical wavelength filtering apparatus with depressed-index claddings
US6552796B2 (en) 2001-04-06 2003-04-22 Lightlab Imaging, Llc Apparatus and method for selective data collection and signal to noise ratio enhancement using optical coherence tomography
US7139598B2 (en) 2002-04-04 2006-11-21 Veralight, Inc. Determination of a measure of a glycation end-product or disease state using tissue fluorescence
US20020158211A1 (en) 2001-04-16 2002-10-31 Dakota Technologies, Inc. Multi-dimensional fluorescence apparatus and method for rapid and highly sensitive quantitative analysis of mixtures
DE10118760A1 (de) 2001-04-17 2002-10-31 Med Laserzentrum Luebeck Gmbh Verfahren zur Ermittlung der Laufzeitverteilung und Anordnung
JP2004528111A (ja) 2001-04-30 2004-09-16 ザ・ジェネラル・ホスピタル・コーポレイション 焦点特性とコヒーレンス・ゲートを制御するために動的フィードバックを用いた、光干渉トモグラフィにおける写像性と感度を改善するための方法及び装置
US7616986B2 (en) 2001-05-07 2009-11-10 University Of Washington Optical fiber scanner for performing multimodal optical imaging
US6615062B2 (en) 2001-05-31 2003-09-02 Infraredx, Inc. Referencing optical catheters
US6701181B2 (en) 2001-05-31 2004-03-02 Infraredx, Inc. Multi-path optical catheter
WO2003003975A2 (en) 2001-06-04 2003-01-16 The General Hospital Corporation Detection and therapy of vulnerable plaque with photodynamic compounds
US6879851B2 (en) 2001-06-07 2005-04-12 Lightlab Imaging, Llc Fiber optic endoscopic gastrointestinal probe
DE10129651B4 (de) 2001-06-15 2010-07-08 Carl Zeiss Jena Gmbh Verfahren zur Kompensation der Dispersion in Signalen von Kurzkohärenz- und/oder OCT-Interferometern
US6702744B2 (en) 2001-06-20 2004-03-09 Advanced Cardiovascular Systems, Inc. Agents that stimulate therapeutic angiogenesis and techniques and devices that enable their delivery
US20040166593A1 (en) 2001-06-22 2004-08-26 Nolte David D. Adaptive interferometric multi-analyte high-speed biosensor
US6685885B2 (en) 2001-06-22 2004-02-03 Purdue Research Foundation Bio-optical compact dist system
DE10137530A1 (de) 2001-08-01 2003-02-13 Presens Prec Sensing Gmbh Anordnung und Verfahren zur Mehrfach-Fluoreszenzmessung
US7061622B2 (en) 2001-08-03 2006-06-13 Case Western Reserve University Aspects of basic OCT engine technologies for high speed optical coherence tomography and light source and other improvements in optical coherence tomography
US20030030816A1 (en) 2001-08-11 2003-02-13 Eom Tae Bong Nonlinearity error correcting method and phase angle measuring method for displacement measurement in two-freqency laser interferometer and displacement measurement system using the same
US6900899B2 (en) 2001-08-20 2005-05-31 Agilent Technologies, Inc. Interferometers with coated polarizing beam splitters that are rotated to optimize extinction ratios
US20030045798A1 (en) 2001-09-04 2003-03-06 Richard Hular Multisensor probe for tissue identification
EP1293925A1 (de) 2001-09-18 2003-03-19 Agfa-Gevaert Verfahren zur Bestimmung von RÖntgenbildern
US6961123B1 (en) 2001-09-28 2005-11-01 The Texas A&M University System Method and apparatus for obtaining information from polarization-sensitive optical coherence tomography
DE10150934A1 (de) 2001-10-09 2003-04-10 Zeiss Carl Jena Gmbh Verfahren und Anordnung zur tiefenaufgelösten Erfassung von Proben
US6980299B1 (en) 2001-10-16 2005-12-27 General Hospital Corporation Systems and methods for imaging a sample
US6658278B2 (en) 2001-10-17 2003-12-02 Terumo Cardiovascular Systems Corporation Steerable infrared imaging catheter having steering fins
US7006231B2 (en) 2001-10-18 2006-02-28 Scimed Life Systems, Inc. Diffraction grating based interferometric systems and methods
US6661513B1 (en) 2001-11-21 2003-12-09 Roygbiv, Llc Refractive-diffractive spectrometer
WO2003053226A2 (en) 2001-12-11 2003-07-03 C2Cure Inc. Apparatus, method and system for intravascular photographic imaging
US20030216719A1 (en) 2001-12-12 2003-11-20 Len Debenedictis Method and apparatus for treating skin using patterns of optical energy
AU2002250917A1 (en) 2001-12-14 2003-06-30 Agilent Technologies, Inc. Retro-reflecting device in particular for tunable lasers
US7736301B1 (en) 2001-12-18 2010-06-15 Advanced Cardiovascular Systems, Inc. Rotatable ferrules and interfaces for use with an optical guidewire
US7365858B2 (en) 2001-12-18 2008-04-29 Massachusetts Institute Of Technology Systems and methods for phase measurements
US6947787B2 (en) 2001-12-21 2005-09-20 Advanced Cardiovascular Systems, Inc. System and methods for imaging within a body lumen
US6975891B2 (en) 2001-12-21 2005-12-13 Nir Diagnostics Inc. Raman spectroscopic system with integrating cavity
EP1324051A1 (de) 2001-12-26 2003-07-02 Kevin R. Forrester Bewegungsmessgerät
US20080154090A1 (en) 2005-01-04 2008-06-26 Dune Medical Devices Ltd. Endoscopic System for In-Vivo Procedures
DE60336534D1 (de) 2002-01-11 2011-05-12 Gen Hospital Corp Vorrichtung zur OCT Bildaufnahme mit axialem Linienfokus für verbesserte Auflösung und Tiefenschärfe
US7072045B2 (en) 2002-01-16 2006-07-04 The Regents Of The University Of California High resolution optical coherence tomography with an improved depth range using an axicon lens
WO2003062802A2 (en) 2002-01-24 2003-07-31 The General Hospital Corporation Apparatus and method for rangings and noise reduction of low coherence interferometry lci and optical coherence tomography (oct) signals by parallel detection of spectral bands
US7355716B2 (en) 2002-01-24 2008-04-08 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
US20040115683A1 (en) * 2002-01-28 2004-06-17 Medford June Iris Analysis of gene expression and biological function using optical imaging
EP1475606A4 (de) 2002-02-14 2007-04-04 Imalux Corp Verfahren zum untersuchen eines objekts und optisches interferometer zur ausführung des verfahrens
US20030165263A1 (en) 2002-02-19 2003-09-04 Hamer Michael J. Histological assessment
US7116887B2 (en) 2002-03-19 2006-10-03 Nufern Optical fiber
US7006232B2 (en) 2002-04-05 2006-02-28 Case Western Reserve University Phase-referenced doppler optical coherence tomography
US7113818B2 (en) 2002-04-08 2006-09-26 Oti Ophthalmic Technologies Inc. Apparatus for high resolution imaging of moving organs
US7016048B2 (en) 2002-04-09 2006-03-21 The Regents Of The University Of California Phase-resolved functional optical coherence tomography: simultaneous imaging of the stokes vectors, structure, blood flow velocity, standard deviation and birefringence in biological samples
US20030236443A1 (en) 2002-04-19 2003-12-25 Cespedes Eduardo Ignacio Methods and apparatus for the identification and stabilization of vulnerable plaque
US7503904B2 (en) 2002-04-25 2009-03-17 Cardiac Pacemakers, Inc. Dual balloon telescoping guiding catheter
JP4135551B2 (ja) 2002-05-07 2008-08-20 松下電工株式会社 ポジションセンサ
JP3834789B2 (ja) 2002-05-17 2006-10-18 独立行政法人科学技術振興機構 自律型超短光パルス圧縮・位相補償・波形整形装置
AU2003245458A1 (en) 2002-06-12 2003-12-31 Advanced Research And Technology Institute, Inc. Method and apparatus for improving both lateral and axial resolution in ophthalmoscopy
US7272252B2 (en) 2002-06-12 2007-09-18 Clarient, Inc. Automated system for combining bright field and fluorescent microscopy
AU2003261158A1 (en) 2002-07-12 2004-02-02 Joe Izatt Method and device for quantitative image correction for optical coherence tomography
JP3950378B2 (ja) 2002-07-19 2007-08-01 新日本製鐵株式会社 同期機
US7283247B2 (en) 2002-09-25 2007-10-16 Olympus Corporation Optical probe system
WO2004029566A1 (en) 2002-09-26 2004-04-08 Bio Techplex Corporation Method and apparatus for screening using a waveform modulated led
US6842254B2 (en) 2002-10-16 2005-01-11 Fiso Technologies Inc. System and method for measuring an optical path difference in a sensing interferometer
US7734332B2 (en) 2002-10-18 2010-06-08 Ariomedica Ltd. Atherectomy system with imaging guidewire
JP4246986B2 (ja) 2002-11-18 2009-04-02 株式会社町田製作所 振動物体観察システム及び声帯観察用処理装置
US6847449B2 (en) 2002-11-27 2005-01-25 The United States Of America As Represented By The Secretary Of The Navy Method and apparatus for reducing speckle in optical coherence tomography images
EP1426799A3 (de) 2002-11-29 2005-05-18 Matsushita Electric Industrial Co., Ltd. Optischer Demultiplexer, optischer Multiplexer/Demultiplexer, und optische Vorrichtung
DE10260256B9 (de) 2002-12-20 2007-03-01 Carl Zeiss Interferometersystem und Meß-/Bearbeitungswerkzeug
GB0229734D0 (en) 2002-12-23 2003-01-29 Qinetiq Ltd Grading oestrogen and progesterone receptors expression
JP4148771B2 (ja) 2002-12-27 2008-09-10 株式会社トプコン 医療機械のレーザ装置
US7123363B2 (en) 2003-01-03 2006-10-17 Rose-Hulman Institute Of Technology Speckle pattern analysis method and system
US7761139B2 (en) 2003-01-24 2010-07-20 The General Hospital Corporation System and method for identifying tissue using low-coherence interferometry
US7075658B2 (en) 2003-01-24 2006-07-11 Duke University Method for optical coherence tomography imaging with molecular contrast
US7643153B2 (en) 2003-01-24 2010-01-05 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
WO2004088361A2 (en) 2003-03-31 2004-10-14 The General Hospital Corporation Speckle reduction in optical coherence tomography by path length encoded angular compounding
US6943892B2 (en) 2003-01-29 2005-09-13 Sarnoff Corporation Instrument having a multi-mode optical element and method
JP4338412B2 (ja) 2003-02-24 2009-10-07 Ｈｏｙａ株式会社 共焦点プローブおよび共焦点顕微鏡
US7271918B2 (en) 2003-03-06 2007-09-18 Zygo Corporation Profiling complex surface structures using scanning interferometry
JP4135550B2 (ja) 2003-04-18 2008-08-20 日立電線株式会社 半導体発光デバイス
US7110109B2 (en) 2003-04-18 2006-09-19 Ahura Corporation Raman spectroscopy system and method and specimen holder therefor
WO2004098396A2 (en) 2003-05-01 2004-11-18 The Cleveland Clinic Foundation Method and apparatus for measuring a retinal sublayer characteristic
WO2004100068A2 (en) 2003-05-05 2004-11-18 D3D, L.P. Optical coherence tomography imaging
CN101785656B (zh) 2003-05-12 2012-08-15 富士胶片株式会社 气囊式内窥镜的气囊控制装置
US7376455B2 (en) 2003-05-22 2008-05-20 Scimed Life Systems, Inc. Systems and methods for dynamic optical imaging
WO2004111929A2 (en) 2003-05-28 2004-12-23 Duke University Improved system for fourier domain optical coherence tomography
EP1644697A4 (de) 2003-05-30 2006-11-29 Univ Duke System und verfahren zur breitband-quadratur-interferometrie mit niedriger kohärenz
US7263394B2 (en) 2003-06-04 2007-08-28 Tomophase Corporation Coherence-gated optical glucose monitor
US6943881B2 (en) 2003-06-04 2005-09-13 Tomophase Corporation Measurements of optical inhomogeneity and other properties in substances using propagation modes of light
EP2011434A3 (de) 2003-06-06 2009-03-25 The General Hospital Corporation Verfahren und Vorrichtung für eine Lichtquelle mit Abstimmung der Wellenlänge
US7458683B2 (en) 2003-06-16 2008-12-02 Amo Manufacturing Usa, Llc Methods and devices for registering optical measurement datasets of an optical system
US7170913B2 (en) 2003-06-19 2007-01-30 Multiwave Photonics, Sa Laser source with configurable output beam characteristics
US20040260182A1 (en) 2003-06-23 2004-12-23 Zuluaga Andres F. Intraluminal spectroscope with wall contacting probe
WO2005017495A2 (en) 2003-08-14 2005-02-24 University Of Central Florida Interferometric sensor for characterizing materials
US7539530B2 (en) 2003-08-22 2009-05-26 Infraredx, Inc. Method and system for spectral examination of vascular walls through blood during cardiac motion
US20050083534A1 (en) 2003-08-28 2005-04-21 Riza Nabeel A. Agile high sensitivity optical sensor
JP2005077964A (ja) 2003-09-03 2005-03-24 Fujitsu Ltd 分光装置
US20050059894A1 (en) 2003-09-16 2005-03-17 Haishan Zeng Automated endoscopy device, diagnostic method, and uses
US20050057680A1 (en) 2003-09-16 2005-03-17 Agan Martin J. Method and apparatus for controlling integration time in imagers
US7935055B2 (en) 2003-09-19 2011-05-03 Siemens Medical Solutions Usa, Inc. System and method of measuring disease severity of a patient before, during and after treatment
US6949072B2 (en) 2003-09-22 2005-09-27 Infraredx, Inc. Devices for vulnerable plaque detection
US7142835B2 (en) 2003-09-29 2006-11-28 Silicon Laboratories, Inc. Apparatus and method for digital image correction in a receiver
CN103284691B (zh) 2003-10-27 2017-04-26 通用医疗公司 用于使用频域干涉测量法进行光学成像的方法和设备
DE10351319B4 (de) 2003-10-31 2005-10-20 Med Laserzentrum Luebeck Gmbh Interferometer für die optische Kohärenztomographie
US7130320B2 (en) 2003-11-13 2006-10-31 Mitutoyo Corporation External cavity laser with rotary tuning element
WO2005054780A1 (en) 2003-11-28 2005-06-16 The General Hospital Corporation Method and apparatus for three-dimensional spectrally encoded imaging
US7359062B2 (en) 2003-12-09 2008-04-15 The Regents Of The University Of California High speed spectral domain functional optical coherence tomography and optical doppler tomography for in vivo blood flow dynamics and tissue structure
DE10358735B4 (de) 2003-12-15 2011-04-21 Siemens Ag Kathetereinrichtung umfassend einen Katheter, insbesondere einen intravaskulären Katheter
US7145661B2 (en) 2003-12-31 2006-12-05 Carl Zeiss Meditec, Inc. Efficient optical coherence tomography (OCT) system and method for rapid imaging in three dimensions
EP1722669A4 (de) 2004-02-27 2009-05-27 Optiscan Pty Ltd Optisches element
US7242480B2 (en) 2004-05-14 2007-07-10 Medeikon Corporation Low coherence interferometry for detecting and characterizing plaques
US7190464B2 (en) 2004-05-14 2007-03-13 Medeikon Corporation Low coherence interferometry for detecting and characterizing plaques
US20050254059A1 (en) 2004-05-14 2005-11-17 Alphonse Gerard A Low coherence interferometric system for optical metrology
AU2004320269B2 (en) 2004-05-29 2011-07-21 The General Hospital Corporation Process, system and software arrangement for a chromatic dispersion compensation using reflective layers in optical coherence tomography (OCT) imaging
EP1771755B1 (de) 2004-07-02 2016-09-21 The General Hospital Corporation Endoskopische darstellungssonde mit doppelt kaschierter faser
DE102004035269A1 (de) 2004-07-21 2006-02-16 Rowiak Gmbh Laryngoskop mit OCT
US7365859B2 (en) 2004-09-10 2008-04-29 The General Hospital Corporation System and method for optical coherence imaging
EP1804638B1 (de) 2004-09-29 2012-12-19 The General Hospital Corporation System und verfahren zur abbildung optischer kohärenz
US7113625B2 (en) 2004-10-01 2006-09-26 U.S. Pathology Labs, Inc. System and method for image analysis of slides
SE0402435L (sv) 2004-10-08 2006-04-09 Trajan Badju Förfarande och system för alstring av tredimensionella bilder
BRPI0517442A (pt) * 2004-10-22 2008-10-07 Fermiscan Australia Pty Ltd método e aparelho analìtico
EP1819270B1 (de) 2004-10-29 2012-12-19 The General Hospital Corporation Polarisationsempfindliche optische kohärenztomographie
US7382949B2 (en) 2004-11-02 2008-06-03 The General Hospital Corporation Fiber-optic rotational device, optical system and method for imaging a sample
US7417740B2 (en) 2004-11-12 2008-08-26 Medeikon Corporation Single trace multi-channel low coherence interferometric sensor
GB0425419D0 (en) 2004-11-18 2004-12-22 Sira Ltd Interference apparatus and method and probe
WO2006058187A2 (en) 2004-11-23 2006-06-01 Robert Eric Betzig Optical lattice microscopy
GB0426609D0 (en) 2004-12-03 2005-01-05 Ic Innovations Ltd Analysis
JP2006162366A (ja) 2004-12-06 2006-06-22 Fujinon Corp 光断層映像装置
US7450242B2 (en) 2004-12-10 2008-11-11 Fujifilm Corporation Optical tomography apparatus
US7336366B2 (en) 2005-01-20 2008-02-26 Duke University Methods and systems for reducing complex conjugate ambiguity in interferometric data
US7342659B2 (en) 2005-01-21 2008-03-11 Carl Zeiss Meditec, Inc. Cross-dispersed spectrometer in a spectral domain optical coherence tomography system
US7330270B2 (en) 2005-01-21 2008-02-12 Carl Zeiss Meditec, Inc. Method to suppress artifacts in frequency-domain optical coherence tomography
HU227859B1 (en) 2005-01-27 2012-05-02 E Szilveszter Vizi Real-time 3d nonlinear microscope measuring system and its application
US7267494B2 (en) 2005-02-01 2007-09-11 Finisar Corporation Fiber stub for cladding mode coupling reduction
US7860555B2 (en) 2005-02-02 2010-12-28 Voyage Medical, Inc. Tissue visualization and manipulation system
US7664300B2 (en) 2005-02-03 2010-02-16 Sti Medical Systems, Llc Uterine cervical cancer computer-aided-diagnosis (CAD)
EP1850735A2 (de) * 2005-02-10 2007-11-07 Lightlab Imaging, Inc. Optische kohärenztomografievorrichtung und -verfahren
US7649160B2 (en) 2005-02-23 2010-01-19 Lyncee Tec S.A. Wave front sensing method and apparatus
JP4628820B2 (ja) 2005-02-25 2011-02-09 サンテック株式会社 波長走査型ファイバレーザ光源
US7530948B2 (en) 2005-02-28 2009-05-12 University Of Washington Tethered capsule endoscope for Barrett's Esophagus screening
JP2008538612A (ja) 2005-04-22 2008-10-30 ザ ジェネラル ホスピタル コーポレイション スペクトルドメイン偏光感受型光コヒーレンストモグラフィを提供することの可能な構成、システム、及び方法
WO2006116362A2 (en) 2005-04-25 2006-11-02 The Trustees Of Boston University Structured substrates for optical surface profiling
WO2006124860A1 (en) 2005-05-13 2006-11-23 The General Hospital Corporation Arrangements, systems and methods capable of providing spectral-domain optical coherence reflectometry for a sensitive detection of chemical and biological sample
WO2006130797A2 (en) 2005-05-31 2006-12-07 The General Hospital Corporation Spectral encoding heterodyne interferometry techniques for imaging
WO2006130802A2 (en) 2005-06-01 2006-12-07 The General Hospital Corporation Apparatus, method and system for performing phase-resolved optical frequency domain imaging
US7391520B2 (en) 2005-07-01 2008-06-24 Carl Zeiss Meditec, Inc. Fourier domain optical coherence tomography employing a swept multi-wavelength laser and a multi-channel receiver
JP4376837B2 (ja) 2005-08-05 2009-12-02 サンテック株式会社 波長走査型レーザ光源
US7668342B2 (en) 2005-09-09 2010-02-23 Carl Zeiss Meditec, Inc. Method of bioimage data processing for revealing more meaningful anatomic features of diseased tissues
KR100743591B1 (ko) 2005-09-23 2007-07-27 한국과학기술원 사이드 로브가 제거된 공초점 자가 간섭 현미경
EP2275026A1 (de) 2005-09-29 2011-01-19 The General Hospital Corporation Anordnungen und Verfahren zur Bereitstellung multimodaler mikroskopischer Darstellung einer oder mehrerer biologischen Strukturen
US7400410B2 (en) 2005-10-05 2008-07-15 Carl Zeiss Meditec, Inc. Optical coherence tomography for eye-length measurement
US7545504B2 (en) 2005-10-07 2009-06-09 Biotigen, Inc. Imaging systems using unpolarized light and related methods and controllers
US7636168B2 (en) 2005-10-11 2009-12-22 Zygo Corporation Interferometry method and system including spectral decomposition
CA2786755C (en) 2005-10-11 2017-06-20 Duke University Systems and method for endoscopic angle-resolved low coherence interferometry
US7408649B2 (en) 2005-10-26 2008-08-05 Kla-Tencor Technologies Corporation Method and apparatus for optically analyzing a surface
WO2007084903A2 (en) 2006-01-19 2007-07-26 The General Hospital Corporation Apparatus for obtaining information for a structure using spectrally-encoded endoscopy techniques and method for producing one or more optical arrangements
US20070223006A1 (en) 2006-01-19 2007-09-27 The General Hospital Corporation Systems and methods for performing rapid fluorescence lifetime, excitation and emission spectral measurements
EP1973466B1 (de) 2006-01-19 2021-01-06 The General Hospital Corporation Ballonbildgebungskatheter
GB0601183D0 (en) 2006-01-20 2006-03-01 Perkinelmer Ltd Improvements in and relating to imaging
EP1988825B1 (de) 2006-02-08 2016-12-21 The General Hospital Corporation Anordnungen und systeme zum abrufen von informationen im zusammenhang mit einer anatomischen probe mithilfe eines optischen mikroskops
US20070191682A1 (en) * 2006-02-15 2007-08-16 Jannick Rolland Optical probes for imaging narrow vessels or lumens
US8184367B2 (en) 2006-02-15 2012-05-22 University Of Central Florida Research Foundation Dynamically focused optical instrument
DE102006008990B4 (de) 2006-02-23 2008-05-21 Atmos Medizintechnik Gmbh & Co. Kg Verfahren und Anordnung zur Erzeugung eines dem Öffnungszustand der Stimmlippen des Kehlkopfes entsprechenden Signals
WO2007106075A2 (en) * 2006-03-03 2007-09-20 University Of Washington Multi-cladding optical fiber scanner
JP2007271761A (ja) 2006-03-30 2007-10-18 Fujitsu Ltd 分光装置および波長分散制御装置
WO2007118129A1 (en) 2006-04-05 2007-10-18 The General Hospital Corporation Methods, arrangements and systems for polarization-sensitive optical frequency domain imaging of a sample
US7719692B2 (en) 2006-04-28 2010-05-18 Bioptigen, Inc. Methods, systems and computer program products for optical coherence tomography (OCT) using automatic dispersion compensation
US7782464B2 (en) 2006-05-12 2010-08-24 The General Hospital Corporation Processes, arrangements and systems for providing a fiber layer thickness map based on optical coherence tomography images
EP1859727A1 (de) 2006-05-26 2007-11-28 Stichting voor de Technische Wetenschappen Optische Triggervorrichtung für Stroboskopie und stroboskopische Vorrichtung
US7599074B2 (en) 2006-06-19 2009-10-06 The Board Of Trustees Of The Leland Stanford Junior University Grating angle magnification enhanced angular sensor and scanner
US20070291277A1 (en) 2006-06-20 2007-12-20 Everett Matthew J Spectral domain optical coherence tomography system
JP5507247B2 (ja) 2006-08-28 2014-05-28 サーモ エレクトロン サイエンティフィック インストルメンツ リミテッド ライアビリティ カンパニー 画像駆動分析による分光器顕微鏡法
US8838213B2 (en) 2006-10-19 2014-09-16 The General Hospital Corporation Apparatus and method for obtaining and providing imaging information associated with at least one portion of a sample, and effecting such portion(s)
WO2008052155A2 (en) 2006-10-26 2008-05-02 Cornell Research Foundation, Inc. System for producing optical pulses of a desired wavelength using cherenkov radiation
US20080204762A1 (en) 2007-01-17 2008-08-28 Duke University Methods, systems, and computer program products for removing undesired artifacts in fourier domain optical coherence tomography (FDOCT) systems using integrating buckets
JP5509417B2 (ja) 2007-03-26 2014-06-04 国立大学法人東京海洋大学 魚類のＶａｓａ遺伝子を用いた生殖細胞マーカー
US8244334B2 (en) 2007-04-10 2012-08-14 University Of Southern California Methods and systems for blood flow measurement using doppler optical coherence tomography
US7799558B1 (en) * 2007-05-22 2010-09-21 Dultz Shane C Ligand binding assays on microarrays in closed multiwell plates
WO2009039303A1 (en) * 2007-09-19 2009-03-26 State University Of New York At Stony Brook Optical coherence tomography systems and methods
US20090131801A1 (en) 2007-10-12 2009-05-21 The General Hospital Corporation Systems and processes for optical imaging of luminal anatomic structures
US8983580B2 (en) * 2008-01-18 2015-03-17 The Board Of Trustees Of The University Of Illinois Low-coherence interferometry and optical coherence tomography for image-guided surgical treatment of solid tumors
US7751057B2 (en) 2008-01-18 2010-07-06 The Board Of Trustees Of The University Of Illinois Magnetomotive optical coherence tomography
US9332942B2 (en) * 2008-01-28 2016-05-10 The General Hospital Corporation Systems, processes and computer-accessible medium for providing hybrid flourescence and optical coherence tomography imaging
JP5192247B2 (ja) 2008-01-29 2013-05-08 並木精密宝石株式会社 Ｏｃｔプローブ
US7898656B2 (en) 2008-04-30 2011-03-01 The General Hospital Corporation Apparatus and method for cross axis parallel spectroscopy
US8184298B2 (en) 2008-05-21 2012-05-22 The Board Of Trustees Of The University Of Illinois Spatial light interference microscopy and fourier transform light scattering for cell and tissue characterization
JP5324839B2 (ja) 2008-06-19 2013-10-23 株式会社トプコン 光画像計測装置
JP5546112B2 (ja) 2008-07-07 2014-07-09 キヤノン株式会社 眼科撮像装置および眼科撮像方法
US8133127B1 (en) 2008-07-21 2012-03-13 Synder Terrance W Sports training device and methods of use
US8599383B2 (en) * 2009-05-06 2013-12-03 The Regents Of The University Of California Optical cytometry
BR112012001042A2 (pt) 2009-07-14 2016-11-22 Gen Hospital Corp equipamento e método de medição do fluxo de fluído dentro de estrutura anatômica.
EP3425439A1 (de) 2010-01-06 2019-01-09 Ecole Polytechnique Federale De Lausanne (EPFL) EPFL-TTO Mikroskopie mit optischer dunkelfeldkohärenz
KR101522850B1 (ko) 2010-01-14 2015-05-26 삼성전자주식회사 움직임 벡터를 부호화, 복호화하는 방법 및 장치
US8792102B2 (en) * 2010-10-28 2014-07-29 General Electric Company Interferometric spectral imaging of a two-dimensional array of samples using surface plasmon resonance
EP2632731B1 (de) 2010-10-29 2015-06-03 Hewlett-Packard Development Company, L.P. Fotopapier
WO2014027320A1 (en) 2012-08-14 2014-02-20 Intertechnique Improved utilization for aircraft airstair space and fuel cell system integration

Also Published As

Publication number Publication date
EP2748587B1 (de) 2021-01-13
WO2013029047A1 (en) 2013-02-28
EP3835718A1 (de) 2021-06-16
US20150253240A1 (en) 2015-09-10
EP2748587A1 (de) 2014-07-02
US10942112B2 (en) 2021-03-09
US10241028B2 (en) 2019-03-26
US20190285539A1 (en) 2019-09-19
EP2748587A4 (de) 2015-05-27

Similar Documents

Publication Publication Date Title
US10942112B2 (en) Methods, systems, arrangements and computer-accessible medium for providing micro-optical coherence tomography procedures
Manfrini et al. Sources of error and interpretation of plaque morphology by optical coherence tomography
Thiberville et al. Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy
Walther et al. Optical coherence tomography in biomedical research
Leitgeb et al. Multimodal optical medical imaging concepts based on optical coherence tomography
Hou et al. Recent advances in optical coherence tomography for the diagnoses of lung disorders
Jing et al. Visualization and detection of ciliary beating pattern and frequency in the upper airway using phase resolved Doppler optical coherence tomography
Baugh et al. Non-destructive two-photon excited fluorescence imaging identifies early nodules in calcific aortic-valve disease
JP2009502393A (ja) 光干渉断層撮影技術の改良ならびに同技術に関連する改良
US20200245905A1 (en) Mapping ciliary activity using phase resolved spectrally encoded interferometric microscopy
McLaughlin et al. Optical coherence tomography in respiratory science and medicine: from airways to alveoli
CN105342568A (zh) 联合相位和幅值的光学相干造影方法及系统
JP2009545737A (ja) 蛍光ベースのＤＮＡイメージサイメトリーを用いたｉｎｖｉｖｏでの癌の検出及び／又は診断方法
US20230280271A1 (en) System and method of dynamic micro-optical coherence tomography for mapping cellular functions
Mukherjee et al. Label-free functional and structural imaging of liver microvascular complex in mice by Jones matrix optical coherence tomography
Li et al. Blood vessel tail artifacts suppression in optical coherence tomography angiography
Quansah et al. Intestinal epithelial barrier integrity investigated by label-free techniques in ulcerative colitis patients
Winkler et al. Quantitative tool for rapid disease mapping using optical coherence tomography images of azoxymethane-treated mouse colon
He et al. Spatial mapping of tracheal ciliary beat frequency using real time phase-resolved Doppler spectrally encoded interferometric microscopy
Wittig et al. Optical coherence tomography for tissue classification of the larynx in an outpatient setting‐a translational challenge on the verge of a resolution?
Miao et al. Phase-resolved dynamic wavefront imaging of cilia metachronal waves
Long et al. Light-sheet laser speckle imaging for cilia motility assessment
Meira-Freitas et al. Advances in the structural evaluation of glaucoma with optical coherence tomography
Blackmon et al. Diffusion-sensitive optical coherence tomography for real-time monitoring of mucus thinning treatments
Alam et al. SSOCT/A reveals cerebrovascular activity during ischemic stroke in zebrafish

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED

AC Divisional application: reference to earlier application

Ref document number: 2748587

Country of ref document: EP

Kind code of ref document: P

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20211216

RBV Designated contracting states (corrected)

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20230316

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230526

AC Divisional application: reference to earlier application

Ref document number: 2748587

Country of ref document: EP

Kind code of ref document: P

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602012079905

Country of ref document: DE

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG9D

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20230726

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1592375

Country of ref document: AT

Kind code of ref document: T

Effective date: 20230726

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20231027

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20231126

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20231127

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20231026

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20231126

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20231027

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230827

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602012079905

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230827

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230831

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20230831

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20240429

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230827

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230827

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20230831

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20240828

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20240827

Year of fee payment: 13

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20240826

Year of fee payment: 13

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20230726